Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumo...Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these cells.CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies.Additionally,the metabolic properties of cancer cells differ markedly from those of normal cells.The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells.Metabolic targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer cells.Thus,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.展开更多
Lung cancer is one of the most common malignant tumors,and its morbidity and mortality are relatively high.Especially for small cell lung cancer(SCLC),the mortality rate is between 80-90%.Unfortunately,more than 50%of...Lung cancer is one of the most common malignant tumors,and its morbidity and mortality are relatively high.Especially for small cell lung cancer(SCLC),the mortality rate is between 80-90%.Unfortunately,more than 50%of lung cancer patients are diagnosed at an advanced stage.The traditional treatment for advanced non-small cell lung cancer(NSCLC)is chemotherapy.In recent years,with the rapid development of molecular pathology,we have a deeper understanding of the underlying pathological mechanism and heterogeneity of lung cancer,especially NSCLC.Molecular targeted therapy is more accurate because of its anti-tumor effect,and the incidence of adverse drug reactions is low.Compared with chemotherapy in the traditional sense,the degree of damage to normal tissues is also significantly reduced.Therefore,it has become a research hotspot in recent years.This article reviews the research progress of various molecular targeted drugs for the treatment of lung cancer based on domestic and foreign research literature and related data.展开更多
Primary liver cancer is one of the commonest causes of death.Hepatocellular carcinoma(HCC) accounts for 90% of primary liver cancers.For patients with unresectable or metastatic HCC,conventional chemotherapy is of lim...Primary liver cancer is one of the commonest causes of death.Hepatocellular carcinoma(HCC) accounts for 90% of primary liver cancers.For patients with unresectable or metastatic HCC,conventional chemotherapy is of limited or no benefit.Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit,leading to an era of targeted agents.Many clinical trials of targeted drugs have been carried out with many more in progress.Some drugs like PTK787 showed potential benefits in the treatment of HCC.Despite these promising breakthroughs,patients with HCC still have a dismal prognosis.Recently,both a phase Ⅲ trial of everolimus and a phase Ⅱ clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC.Sorafenib still plays a pivotal role in advanced HCC,leading to further explorations to exert its maximum efficacy.Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances.New targeted agents such as mammalian target of rapamycin inhibitors are under investigation,as well as further exploration of the mechanism of hepatocarcinogenesis.展开更多
Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these app...Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.展开更多
BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a...BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a 17-year-old female patient presenting with in-termittent,non-cyclical vaginal bleeding and associated lower abdominal pain.Pelvic magnetic resonance imaging and additional examinations led to the dia-gnosis of cervical rhabdomyosarcoma.The primary treatment options for uterine cervical rhabdomyosarcoma include surgery,with or without adjuvant chemo-therapy and radiotherapy.This patient underwent surgery followed by a posto-perative chemotherapy regimen of gemcitabine combined with docetaxel and bevacizumab.After 19 months of follow-up,the patient showed no signs of re-currence and maintained good overall health.Given the rarity of cervix rhab-domyosarcoma,this case is presented to provide insights into the diagnosis and treatment of this condition.CONCLUSION This suggests that bevacizumab may demonstrate potential efficacy in the treat-ment of cervical rhabdomyosarcoma.In the future,targeted therapy is expected to play an increasingly significant role in the management of rhabdomyosarcoma.展开更多
Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms...Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms, requiring histopathology for diagnosis. Surgery remains the standard of care for localized disease, serving both diagnostic and therapeutic purposes, though adjuvant chemotherapy has shown limited efficacy. In metastatic CDC, the gemcitabine-cisplatin regimen is commonly used due to its resemblance to urothelial cancer and supportive data from prospective studies. Newer therapies offer promise in advanced cases. Immune checkpoint inhibitors, such as nivolumab alone or with ipilimumab, have shown benefits in patients with high PD-L1 expression. Targeted therapies like cabozantinib demonstrated efficacy and safety as first-line treatments in phase II trials, while sunitinib and sorafenib have shown responses in various case reports and cohorts. However, combining chemotherapy with bevacizumab did not improve outcomes in phase II trials. Despite therapeutic advances in urothelial cancers and clear cell renal tumors, the CDC entity remains a challenging malignancy, emphasizing the need for continued research to understand the true efficacy of treatment and to prolong survival in advanced disease.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantati...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.展开更多
Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown pr...Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.展开更多
BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and progno...BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.展开更多
Colon-targeted oral drug delivery systems are one of the most promising therapeutic strategies for alleviating and curing inflammatory bowel disease(IBD),but they still face challenges in successfully passing through ...Colon-targeted oral drug delivery systems are one of the most promising therapeutic strategies for alleviating and curing inflammatory bowel disease(IBD),but they still face challenges in successfully passing through the harsh gastrointestinal environment and intestinal mucus barrier.To overcome the gastrointestinal barriers for oral drug delivery mentioned above,a“spore-like”oral nanodrug delivery platform(Cur/COS/SC NPs)has been developed.Firstly,chitooligosaccharides(COS)are encapsulated on the surface of Curcumin nanoparticles(Cur NPs)to form carrier-free nanoparticles(Cur/COS NPs).Subsequently,inspired by the natural high resistance of spore coat(SC),SC is chosen as the“protective umbrella”to encapsulate Cur/COS NPs for precision targeted therapy of IBD.After oral administration,SC can effectively protect NPs through the rugged gastrointestinal environment and exhibit excellent intestinal mucus penetration characteristics.Moreover,the negatively-charged Cur/COS/SC NPs specifically target positivelycharged inflamed colon via electrostatic interactions.It is demonstrated that Cur/COS/SC NPs can promote the expression of tight junction proteins,inhibit aberrant activation of the Toll-like receptor 4/myeloid differentiation primary response gene 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway,and downregulate the levels of pro-inflammatory factors,exhibiting excellent anti-inflammatory effects.Notably,it is found that Cur/COS/SC NPs can significantly increase the richness and diversity of gut microbiota,and restore the homeostasis of gut microbiota by inhibiting pathogenic bacteria and promoting probiotics.Hence,Cur/COS/SC NPs provide a safe,efficient,and feasible new strategy for IBD treatment.展开更多
Hemoptysis is a severe complication of pulmonary hypertension (PH) with a low in- cidence of 6%-11%.^([1-4])Although occurring in all forms of PH,it is more commonly seen in pulmonary arterial hypertension (PAH),assoc...Hemoptysis is a severe complication of pulmonary hypertension (PH) with a low in- cidence of 6%-11%.^([1-4])Although occurring in all forms of PH,it is more commonly seen in pulmonary arterial hypertension (PAH),associated with congenital heart disease (PAH-CHD).^([5,6])Since enlarged bronchial arteries are a frequent source of pulmonary bleeding,the primary treatment focuses on bronchial artery embolization (BAE),especially for chronic thromboembolic pulmonary hypertension (CTEPH) patients^([7,8]).However,there is disagreement regarding medical therapy,which has received little attention in the recently published PH guidelines.^([5,6])展开更多
BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings....BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings.The combination of targeted therapies with immune checkpoint inhibitors(ICIs)has shown potential in addressing the limitations of single-agent treatments.AIM To evaluate the efficacy and safety of targeted therapy(TT)alone and in combination with ICIs for metastatic CRC(mCRC).METHODS A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC.A total of 99 patients treated with regorafenib or fruquintinib,with or without ICIs,were enrolled.Propensity score matching(PSM)and inverse probability weighting(IPW)were employed to balance baseline characteristics.The primary endpoint was progression-free survival(PFS),while overall survival(OS)and safety were secondary.RESULTS Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses(original:6.0 vs 3.4 months,P<0.01;PSM:6.15 vs 4.25 months,P<0.05;IPW:5.6 vs 3.3 months,P<0.01).Although the median OS showed a trend toward improvement in the combination group,the difference was insignificant.Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression(hazard ratio=0.38,P<0.001).Adverse events(AEs)were generally manageable with both regimens,while serious AEs(grade 3-4)were primarily hypertension,fatigue,and reduced platelet counts.All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug,and no treatment-related deaths were observed.CONCLUSION The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC,accompanied by a favorable safety profile.These findings underscore the benefits of combination therapy in this setting,warranting further investigation in larger prospective clinical trials.展开更多
Glycyrrhetinic acid(GA)sheds new light on liver-targeted therapy due to high-specific accumulation to GA receptors in liver,however,the limitation of commonly used macromolecular GA modification approaches as well as ...Glycyrrhetinic acid(GA)sheds new light on liver-targeted therapy due to high-specific accumulation to GA receptors in liver,however,the limitation of commonly used macromolecular GA modification approaches as well as the application gap across various vector have constrained its use.In this study,we proposed a novel perspective to break out,disulfide bonds(SS)were employed as linkage to facilitate GA modification,which allowed further connections with various carriers,while provided additional glutathione(GSH)-responsive property.The superiority of GA-disulfide conjunction was validated using mesoporous silica nanoparticles(MSN)as model carriers,chemotherapeutic drug(doxorubicin)and photosensitizer(indocyanine green)were loaded into MSN-SS-GA to further achieve chemo-photothermal synergistic anti-tumor therapy.Based on results from multiple evaluations,the GA-disulfide drafted MSN(DI/MSN-SS-GA)demonstrated expected liver tumor targeting effect and exhibited GSH-stimuli release property to reduce preleakage.Taken together,this study presents an effective chemo-photothermal therapy for liver cancer(88.26%),offers a potential,robust and straightforward strategy on GA application for enhancing liver targeting therapy.展开更多
BACKGROUND Targeted therapy combined with anti-programmed cell death 1 immunotherapy(TP)and trifluridine/tipiracil(TAS-102)combined with bevacizumab(TB)are two common therapies for patients with late-line therapy in m...BACKGROUND Targeted therapy combined with anti-programmed cell death 1 immunotherapy(TP)and trifluridine/tipiracil(TAS-102)combined with bevacizumab(TB)are two common therapies for patients with late-line therapy in microsatellite stable(MSS)metastatic colorectal cancer(mCRC).However,it is still unclear which therapy can bring better prognosis.AIM To evaluate the effectiveness and safety of TP vs TB as the late-line regimen for MSS mCRC in the real world.METHODS This is a dual-center retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital.Patients with MSS mCRC who had received at least the second line treatment were eligible.Propensity score(PS)would be calculated to balance the baseline characteristics of two cohorts.Progression-free survival(PFS)was set as the primary endpoint.The Kaplan-Meier method and Cox proportional hazard model were used to evaluate PFS and to estimate hazard ratios(HRs)and 95%confidence intervals(CIs).Landmark analysis was performed to create segmented survival curves,studying the impact of treatment regimen on prognosis during different follow-up periods.RESULTS Between July 2019 and March 2025(data cutoff),127 eligible patients were enrolled,with 88 and 39 patients assigned to the TP and TB cohorts,respectively,based on treatment allocation.At a global median follow-up of 9.73 months,the crude median PFS was 3.9 months(95%CI:3.03-5.53)in the TP cohort vs 4.17 months(95%CI:2.87-5.6)in the TB cohort,yielding a nonsignificant HR of 1.43(95%CI:0.94-2.18,P=0.092;TB as reference).Multivariate Cox regression analysis,adjusted for sex,age>60 years,Eastern Cooperative Oncology Group performance status,RAS mutation,primary tumor location(left vs right),number of metastatic organs(liver/lung),and treatment line(≥3rd line),demonstrated an adjusted HR of 1.23(95%CI:0.80-1.88,P=0.348).PS-based analyses using three methodologies:Inverse probability weighting,PS matching(post-matching n=55 vs 30),and PS-adjusted multivariate Cox regression.These analyses revealed consistent nonsignificant trends favoring TB,with HRs for TP of 1.26(95%CI:0.76-2.10,P=0.077),1.42(95%CI:0.87-2.34,P=0.164),and 1.26(95%CI:0.76-2.10,P=0.367),respectively.Notably,landmark PFS analyses at 90,120,and 150 days demonstrated a significantly higher proportion of TP patients maintaining disease control beyond these timepoints(P=0.048,0.031,and 0.035,respectively),suggesting sustained clinical benefits in TP responders.CONCLUSION TP and TB demonstrated similar PFS in both crude and PS-adjusted analyses.However,patients who derived benefits from TP therapy exceeding 90 days showed more sustained clinical advantages compared to TB.Our study suggests that for patients with MSS mCRC who respond to TP therapy in later-line treatments,this regimen could provide additional prolonged clinical benefits,which warrants further validation through large-scale cohort investigations.展开更多
BACKGROUND The incidence of colon cancer has been progressively increasing over time,whereas penile metastasis of colon cancer has remained exceedingly uncommon.Since the prognosis for colon cancer with BRAF_(V600E)mu...BACKGROUND The incidence of colon cancer has been progressively increasing over time,whereas penile metastasis of colon cancer has remained exceedingly uncommon.Since the prognosis for colon cancer with BRAF_(V600E)mutation is relatively unfavorable,further exploration and investigation are still required to develop treatment strategies for such rare cases.CASE SUMMARY About one year after surgery and chemotherapy,a 50-year-old patient with sigmoid colon cancer developed a mass at the base of the patient's penis,accompanied by severe tenderness and pain during urination.With disease progression,multiple metastatic nodules also emerged in other regions of the penis,including the coronal sulcus.The nodules located in the coronal sulcus were excised for histopathological examination.The histopathological findings revealed that the nodules were metastases originating from the sigmoid colon cancer,with a BRAF V600E mutation detected.This prompted a modification of the therapy regimen of cetuximab,dabrafenib and trametinib,which effectively held back the progression of penile metastasis in the patient.CONCLUSION Combining the BRAF/MEK-targeted therapy with cetuximab demonstrates a favorable therapeutic response in BRAF_(V600E)-mutated colon cancer with penile metastasis.展开更多
SHP2 is the first identified oncogenic tyrosine phosphatase that promotes colorectal cancer(CRC)progression,and it is consistently overexpressed in CRC.It facilitates CRC oncogenesis by mediating downstream signaling ...SHP2 is the first identified oncogenic tyrosine phosphatase that promotes colorectal cancer(CRC)progression,and it is consistently overexpressed in CRC.It facilitates CRC oncogenesis by mediating downstream signaling cascades of receptor tyrosine kinases,including the RAS/ERK,JAK/STAT,and PI3K/AKT pathways,which are clinically associated with poor prognosis.Furthermore,SHP2 orchestrates immunosuppressive signaling networks by impairing cytotoxic T cell infiltration and changing the phenotype of tumor-associated macrophages within the tumor microenvironment(TME).Targeting SHP2 represents a dual therapeutic strategy in CRC:It concurrently regulates RTK signaling and reprograms the immunosuppressive TME.SHP2 inhibitors,administered both as monotherapy and in combination regimens,have advanced into clinical trial phases.Consequently,SHP2 serves as both a molecular target for precision oncology and an immunomodulatory node,positioning it as a high-priority candidate for CRC treatment.展开更多
Synovial sarcoma is a high-grade soft tissue malignancy characterized by a unique fusion gene known as SS18-SSX.The SS18-SSX fusion protein acts as an oncogenic driver of synovial sarcoma,and it has thus been commonly...Synovial sarcoma is a high-grade soft tissue malignancy characterized by a unique fusion gene known as SS18-SSX.The SS18-SSX fusion protein acts as an oncogenic driver of synovial sarcoma,and it has thus been commonly accepted that disruption of SS18-SSX function represents a therapeutic means of treating synovial sarcoma,but emerging evidence suggests that upon depletion of SS18-SSX,an anti-apoptotic signal surprisingly arises to protect synovial sarcoma cell survival.In this article,we discuss the controversial roles of SS18-SSX’s transcriptional activity in synovial sarcoma biology and outline a synergistic strategy for overcoming the resistance of synovial sarcoma cells to SS18-SSX targeted therapeutics.展开更多
Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address t...Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address this issue,advances have been made in therapies targeting molecular pathways related to the murine double minute 2 protooncogene(MDM2)-tumor proteinp53(TP53)interaction.This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells,as evidenced by clinical studies,reviews,and trials.TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53.MDM2 and TP53 activity is tightly regulated.However,cancerous breast cells overexpress MDM2 through five hypothesized mechanisms.Consequently,TP53 levels decrease with increased tumor cell proliferation.Three strategies have been identified for controlling MDM2 upregulation in cells with wild-type or mutated TP53.MDM2 inhibitors(MDM2i)are administered in combination with existing chemotherapies to reduce their effects on healthy cells.Few clinical and preclinical studies have been conducted using MDM2i,which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.展开更多
[Objectives]This study was conducted to explore the curative effect of Qingfei Ditan decoction combined with targeted drug penetration therapy of traditional Chinese medicine on severe mycoplasma pneumonia in children...[Objectives]This study was conducted to explore the curative effect of Qingfei Ditan decoction combined with targeted drug penetration therapy of traditional Chinese medicine on severe mycoplasma pneumonia in children.[Methods]Based on the retrospective study method,children with severe mycoplasma pneumonia admitted to the Children s Hospital of Soochow University from April 2023 to October 2023 were selected,and divided into a treatment group including 56 cases and a control group including 145 cases.The curative effect and adverse reactions of the two groups were compared.[Results]The total effective rate of the treatment group was higher than that of the control group,and the disappearance time of cough and lung rales was shorter than that of the control group,and the incidence of adverse reactions was lower,showing statistical significance(P<0.05).However,defervescence time and bronchoscope flushing rate showed no significant difference(P>0.05).[Conclusions]Qingfei Ditan Decoction combined with targeted drug penetration therapy of traditional Chinese medicine has a significant effect on severe mycoplasma pneumonia in children,and can reduce the side effects of drugs.It is a safe and efficient combination treatment scheme of traditional Chinese medicine.展开更多
Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while add...Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.展开更多
文摘Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these cells.CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies.Additionally,the metabolic properties of cancer cells differ markedly from those of normal cells.The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells.Metabolic targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer cells.Thus,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.
文摘Lung cancer is one of the most common malignant tumors,and its morbidity and mortality are relatively high.Especially for small cell lung cancer(SCLC),the mortality rate is between 80-90%.Unfortunately,more than 50%of lung cancer patients are diagnosed at an advanced stage.The traditional treatment for advanced non-small cell lung cancer(NSCLC)is chemotherapy.In recent years,with the rapid development of molecular pathology,we have a deeper understanding of the underlying pathological mechanism and heterogeneity of lung cancer,especially NSCLC.Molecular targeted therapy is more accurate because of its anti-tumor effect,and the incidence of adverse drug reactions is low.Compared with chemotherapy in the traditional sense,the degree of damage to normal tissues is also significantly reduced.Therefore,it has become a research hotspot in recent years.This article reviews the research progress of various molecular targeted drugs for the treatment of lung cancer based on domestic and foreign research literature and related data.
基金the National Nature Science Foundation of China,Nos.30770971,30800518,81070362,81172470 and 81372629two key projects from the Nature Science Foundation of Hunan Province,Nos.11JJ2049 and 12JJ3118
文摘Primary liver cancer is one of the commonest causes of death.Hepatocellular carcinoma(HCC) accounts for 90% of primary liver cancers.For patients with unresectable or metastatic HCC,conventional chemotherapy is of limited or no benefit.Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit,leading to an era of targeted agents.Many clinical trials of targeted drugs have been carried out with many more in progress.Some drugs like PTK787 showed potential benefits in the treatment of HCC.Despite these promising breakthroughs,patients with HCC still have a dismal prognosis.Recently,both a phase Ⅲ trial of everolimus and a phase Ⅱ clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC.Sorafenib still plays a pivotal role in advanced HCC,leading to further explorations to exert its maximum efficacy.Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances.New targeted agents such as mammalian target of rapamycin inhibitors are under investigation,as well as further exploration of the mechanism of hepatocarcinogenesis.
文摘Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.
文摘BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a 17-year-old female patient presenting with in-termittent,non-cyclical vaginal bleeding and associated lower abdominal pain.Pelvic magnetic resonance imaging and additional examinations led to the dia-gnosis of cervical rhabdomyosarcoma.The primary treatment options for uterine cervical rhabdomyosarcoma include surgery,with or without adjuvant chemo-therapy and radiotherapy.This patient underwent surgery followed by a posto-perative chemotherapy regimen of gemcitabine combined with docetaxel and bevacizumab.After 19 months of follow-up,the patient showed no signs of re-currence and maintained good overall health.Given the rarity of cervix rhab-domyosarcoma,this case is presented to provide insights into the diagnosis and treatment of this condition.CONCLUSION This suggests that bevacizumab may demonstrate potential efficacy in the treat-ment of cervical rhabdomyosarcoma.In the future,targeted therapy is expected to play an increasingly significant role in the management of rhabdomyosarcoma.
文摘Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms, requiring histopathology for diagnosis. Surgery remains the standard of care for localized disease, serving both diagnostic and therapeutic purposes, though adjuvant chemotherapy has shown limited efficacy. In metastatic CDC, the gemcitabine-cisplatin regimen is commonly used due to its resemblance to urothelial cancer and supportive data from prospective studies. Newer therapies offer promise in advanced cases. Immune checkpoint inhibitors, such as nivolumab alone or with ipilimumab, have shown benefits in patients with high PD-L1 expression. Targeted therapies like cabozantinib demonstrated efficacy and safety as first-line treatments in phase II trials, while sunitinib and sorafenib have shown responses in various case reports and cohorts. However, combining chemotherapy with bevacizumab did not improve outcomes in phase II trials. Despite therapeutic advances in urothelial cancers and clear cell renal tumors, the CDC entity remains a challenging malignancy, emphasizing the need for continued research to understand the true efficacy of treatment and to prolong survival in advanced disease.
基金Supported by the National Natural Science Foundation of China,No.82270634Third Affiliated Hospital of Naval Medical University,No.tf2024yzyy01.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.
基金Supported by 2023 Hebei Provincial Medical Scientific Research Project Plan,No.20231304.
文摘Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.
基金Supported by Chongqing Young and Middle-aged Medical High-end Talents,No.YXGD202405Chongqing District and County Head Goose Talents,Chongqing Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.2024ZYYB036Chongqing Banan District Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.BNWJ202300112.
文摘BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.
基金supported by the National Natural Science Foundation of China(Nos.82272847,82304417,82303529,82171333)China Postdoctoral Science Foundation(Nos.2023TQ0307,2023M743231,2023M730971)+2 种基金Science and Technology Project of Henan Province(No.242102311204)Postdoctoral Fellowship Program of CPSF(No.GZB20230675)Modern Analysis and Computer Center of Zhengzhou University.
文摘Colon-targeted oral drug delivery systems are one of the most promising therapeutic strategies for alleviating and curing inflammatory bowel disease(IBD),but they still face challenges in successfully passing through the harsh gastrointestinal environment and intestinal mucus barrier.To overcome the gastrointestinal barriers for oral drug delivery mentioned above,a“spore-like”oral nanodrug delivery platform(Cur/COS/SC NPs)has been developed.Firstly,chitooligosaccharides(COS)are encapsulated on the surface of Curcumin nanoparticles(Cur NPs)to form carrier-free nanoparticles(Cur/COS NPs).Subsequently,inspired by the natural high resistance of spore coat(SC),SC is chosen as the“protective umbrella”to encapsulate Cur/COS NPs for precision targeted therapy of IBD.After oral administration,SC can effectively protect NPs through the rugged gastrointestinal environment and exhibit excellent intestinal mucus penetration characteristics.Moreover,the negatively-charged Cur/COS/SC NPs specifically target positivelycharged inflamed colon via electrostatic interactions.It is demonstrated that Cur/COS/SC NPs can promote the expression of tight junction proteins,inhibit aberrant activation of the Toll-like receptor 4/myeloid differentiation primary response gene 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway,and downregulate the levels of pro-inflammatory factors,exhibiting excellent anti-inflammatory effects.Notably,it is found that Cur/COS/SC NPs can significantly increase the richness and diversity of gut microbiota,and restore the homeostasis of gut microbiota by inhibiting pathogenic bacteria and promoting probiotics.Hence,Cur/COS/SC NPs provide a safe,efficient,and feasible new strategy for IBD treatment.
基金supported by Liaoning Xingliao Talent Project (Grant No. XLYC2007020)。
文摘Hemoptysis is a severe complication of pulmonary hypertension (PH) with a low in- cidence of 6%-11%.^([1-4])Although occurring in all forms of PH,it is more commonly seen in pulmonary arterial hypertension (PAH),associated with congenital heart disease (PAH-CHD).^([5,6])Since enlarged bronchial arteries are a frequent source of pulmonary bleeding,the primary treatment focuses on bronchial artery embolization (BAE),especially for chronic thromboembolic pulmonary hypertension (CTEPH) patients^([7,8]).However,there is disagreement regarding medical therapy,which has received little attention in the recently published PH guidelines.^([5,6])
基金Supported by Hebei Provincial Medical Science Research Project Program,No.20240164.
文摘BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings.The combination of targeted therapies with immune checkpoint inhibitors(ICIs)has shown potential in addressing the limitations of single-agent treatments.AIM To evaluate the efficacy and safety of targeted therapy(TT)alone and in combination with ICIs for metastatic CRC(mCRC).METHODS A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC.A total of 99 patients treated with regorafenib or fruquintinib,with or without ICIs,were enrolled.Propensity score matching(PSM)and inverse probability weighting(IPW)were employed to balance baseline characteristics.The primary endpoint was progression-free survival(PFS),while overall survival(OS)and safety were secondary.RESULTS Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses(original:6.0 vs 3.4 months,P<0.01;PSM:6.15 vs 4.25 months,P<0.05;IPW:5.6 vs 3.3 months,P<0.01).Although the median OS showed a trend toward improvement in the combination group,the difference was insignificant.Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression(hazard ratio=0.38,P<0.001).Adverse events(AEs)were generally manageable with both regimens,while serious AEs(grade 3-4)were primarily hypertension,fatigue,and reduced platelet counts.All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug,and no treatment-related deaths were observed.CONCLUSION The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC,accompanied by a favorable safety profile.These findings underscore the benefits of combination therapy in this setting,warranting further investigation in larger prospective clinical trials.
基金funded by Research Project of Department of Education of Liaoning Province(No.LJKMZ20221363,China)。
文摘Glycyrrhetinic acid(GA)sheds new light on liver-targeted therapy due to high-specific accumulation to GA receptors in liver,however,the limitation of commonly used macromolecular GA modification approaches as well as the application gap across various vector have constrained its use.In this study,we proposed a novel perspective to break out,disulfide bonds(SS)were employed as linkage to facilitate GA modification,which allowed further connections with various carriers,while provided additional glutathione(GSH)-responsive property.The superiority of GA-disulfide conjunction was validated using mesoporous silica nanoparticles(MSN)as model carriers,chemotherapeutic drug(doxorubicin)and photosensitizer(indocyanine green)were loaded into MSN-SS-GA to further achieve chemo-photothermal synergistic anti-tumor therapy.Based on results from multiple evaluations,the GA-disulfide drafted MSN(DI/MSN-SS-GA)demonstrated expected liver tumor targeting effect and exhibited GSH-stimuli release property to reduce preleakage.Taken together,this study presents an effective chemo-photothermal therapy for liver cancer(88.26%),offers a potential,robust and straightforward strategy on GA application for enhancing liver targeting therapy.
基金Supported by the National High Level Hospital Clinical Research Funding(Multi-Center Clinical Research Project of Peking University First Hospital),No.2022CR65.
文摘BACKGROUND Targeted therapy combined with anti-programmed cell death 1 immunotherapy(TP)and trifluridine/tipiracil(TAS-102)combined with bevacizumab(TB)are two common therapies for patients with late-line therapy in microsatellite stable(MSS)metastatic colorectal cancer(mCRC).However,it is still unclear which therapy can bring better prognosis.AIM To evaluate the effectiveness and safety of TP vs TB as the late-line regimen for MSS mCRC in the real world.METHODS This is a dual-center retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital.Patients with MSS mCRC who had received at least the second line treatment were eligible.Propensity score(PS)would be calculated to balance the baseline characteristics of two cohorts.Progression-free survival(PFS)was set as the primary endpoint.The Kaplan-Meier method and Cox proportional hazard model were used to evaluate PFS and to estimate hazard ratios(HRs)and 95%confidence intervals(CIs).Landmark analysis was performed to create segmented survival curves,studying the impact of treatment regimen on prognosis during different follow-up periods.RESULTS Between July 2019 and March 2025(data cutoff),127 eligible patients were enrolled,with 88 and 39 patients assigned to the TP and TB cohorts,respectively,based on treatment allocation.At a global median follow-up of 9.73 months,the crude median PFS was 3.9 months(95%CI:3.03-5.53)in the TP cohort vs 4.17 months(95%CI:2.87-5.6)in the TB cohort,yielding a nonsignificant HR of 1.43(95%CI:0.94-2.18,P=0.092;TB as reference).Multivariate Cox regression analysis,adjusted for sex,age>60 years,Eastern Cooperative Oncology Group performance status,RAS mutation,primary tumor location(left vs right),number of metastatic organs(liver/lung),and treatment line(≥3rd line),demonstrated an adjusted HR of 1.23(95%CI:0.80-1.88,P=0.348).PS-based analyses using three methodologies:Inverse probability weighting,PS matching(post-matching n=55 vs 30),and PS-adjusted multivariate Cox regression.These analyses revealed consistent nonsignificant trends favoring TB,with HRs for TP of 1.26(95%CI:0.76-2.10,P=0.077),1.42(95%CI:0.87-2.34,P=0.164),and 1.26(95%CI:0.76-2.10,P=0.367),respectively.Notably,landmark PFS analyses at 90,120,and 150 days demonstrated a significantly higher proportion of TP patients maintaining disease control beyond these timepoints(P=0.048,0.031,and 0.035,respectively),suggesting sustained clinical benefits in TP responders.CONCLUSION TP and TB demonstrated similar PFS in both crude and PS-adjusted analyses.However,patients who derived benefits from TP therapy exceeding 90 days showed more sustained clinical advantages compared to TB.Our study suggests that for patients with MSS mCRC who respond to TP therapy in later-line treatments,this regimen could provide additional prolonged clinical benefits,which warrants further validation through large-scale cohort investigations.
基金National Natural Science Foundation of China,No.81871981Natural Science Foundation of Guangdong Province,No.2022A1515012348 and No.2023A1515010457.
文摘BACKGROUND The incidence of colon cancer has been progressively increasing over time,whereas penile metastasis of colon cancer has remained exceedingly uncommon.Since the prognosis for colon cancer with BRAF_(V600E)mutation is relatively unfavorable,further exploration and investigation are still required to develop treatment strategies for such rare cases.CASE SUMMARY About one year after surgery and chemotherapy,a 50-year-old patient with sigmoid colon cancer developed a mass at the base of the patient's penis,accompanied by severe tenderness and pain during urination.With disease progression,multiple metastatic nodules also emerged in other regions of the penis,including the coronal sulcus.The nodules located in the coronal sulcus were excised for histopathological examination.The histopathological findings revealed that the nodules were metastases originating from the sigmoid colon cancer,with a BRAF V600E mutation detected.This prompted a modification of the therapy regimen of cetuximab,dabrafenib and trametinib,which effectively held back the progression of penile metastasis in the patient.CONCLUSION Combining the BRAF/MEK-targeted therapy with cetuximab demonstrates a favorable therapeutic response in BRAF_(V600E)-mutated colon cancer with penile metastasis.
基金Supported by Zhejiang Provincial Natural Science Foundation for Youths,No.QN25H160012Zhejiang Medical and Health Science and Technology Plan,No.2023RC006.
文摘SHP2 is the first identified oncogenic tyrosine phosphatase that promotes colorectal cancer(CRC)progression,and it is consistently overexpressed in CRC.It facilitates CRC oncogenesis by mediating downstream signaling cascades of receptor tyrosine kinases,including the RAS/ERK,JAK/STAT,and PI3K/AKT pathways,which are clinically associated with poor prognosis.Furthermore,SHP2 orchestrates immunosuppressive signaling networks by impairing cytotoxic T cell infiltration and changing the phenotype of tumor-associated macrophages within the tumor microenvironment(TME).Targeting SHP2 represents a dual therapeutic strategy in CRC:It concurrently regulates RTK signaling and reprograms the immunosuppressive TME.SHP2 inhibitors,administered both as monotherapy and in combination regimens,have advanced into clinical trial phases.Consequently,SHP2 serves as both a molecular target for precision oncology and an immunomodulatory node,positioning it as a high-priority candidate for CRC treatment.
文摘Synovial sarcoma is a high-grade soft tissue malignancy characterized by a unique fusion gene known as SS18-SSX.The SS18-SSX fusion protein acts as an oncogenic driver of synovial sarcoma,and it has thus been commonly accepted that disruption of SS18-SSX function represents a therapeutic means of treating synovial sarcoma,but emerging evidence suggests that upon depletion of SS18-SSX,an anti-apoptotic signal surprisingly arises to protect synovial sarcoma cell survival.In this article,we discuss the controversial roles of SS18-SSX’s transcriptional activity in synovial sarcoma biology and outline a synergistic strategy for overcoming the resistance of synovial sarcoma cells to SS18-SSX targeted therapeutics.
文摘Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address this issue,advances have been made in therapies targeting molecular pathways related to the murine double minute 2 protooncogene(MDM2)-tumor proteinp53(TP53)interaction.This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells,as evidenced by clinical studies,reviews,and trials.TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53.MDM2 and TP53 activity is tightly regulated.However,cancerous breast cells overexpress MDM2 through five hypothesized mechanisms.Consequently,TP53 levels decrease with increased tumor cell proliferation.Three strategies have been identified for controlling MDM2 upregulation in cells with wild-type or mutated TP53.MDM2 inhibitors(MDM2i)are administered in combination with existing chemotherapies to reduce their effects on healthy cells.Few clinical and preclinical studies have been conducted using MDM2i,which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.
基金Supported by Key project of National Key R&D Program of China in 2022(2022YFC2502700).
文摘[Objectives]This study was conducted to explore the curative effect of Qingfei Ditan decoction combined with targeted drug penetration therapy of traditional Chinese medicine on severe mycoplasma pneumonia in children.[Methods]Based on the retrospective study method,children with severe mycoplasma pneumonia admitted to the Children s Hospital of Soochow University from April 2023 to October 2023 were selected,and divided into a treatment group including 56 cases and a control group including 145 cases.The curative effect and adverse reactions of the two groups were compared.[Results]The total effective rate of the treatment group was higher than that of the control group,and the disappearance time of cough and lung rales was shorter than that of the control group,and the incidence of adverse reactions was lower,showing statistical significance(P<0.05).However,defervescence time and bronchoscope flushing rate showed no significant difference(P>0.05).[Conclusions]Qingfei Ditan Decoction combined with targeted drug penetration therapy of traditional Chinese medicine has a significant effect on severe mycoplasma pneumonia in children,and can reduce the side effects of drugs.It is a safe and efficient combination treatment scheme of traditional Chinese medicine.
文摘Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.
