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
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 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
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 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
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
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
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
Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effect...Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.展开更多
BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more effi...BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.展开更多
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important ...Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.展开更多
Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal ...Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal cancer (EC) patients at advanced or metastatic stages. While historically considered incurable, ongoing advancements in medical research have led to the integration of various treatment modalities as primary approaches for managing advanced endometrial cancer. These modalities include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Notably, the introduction of targeted therapy and immunotherapy has significantly enhanced the survival rates of individuals with EC. Immunotherapy has appeared as the predominant treatment for advanced esophageal cancer, while targeted therapy faces certain obstacles. Consequently, this review primarily focuses on the advancements in targeted therapy for esophageal cancer (EC), evaluating the effectiveness and safety of relevant medications, and aiming to provide guidance for the comprehensive management of EC based on current research findings.展开更多
Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth ...Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth of these cells. In the case of gastric cancer,survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently,several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis,prognosis and treatment of gastric tumors.展开更多
Gastric cancer is the second leading cause of cancerrelated deaths worldwide.Conventional cytotoxic chemotherapy has limited efficacy for metastatic gastric cancer,with an overall survival of approximately ten months....Gastric cancer is the second leading cause of cancerrelated deaths worldwide.Conventional cytotoxic chemotherapy has limited efficacy for metastatic gastric cancer,with an overall survival of approximately ten months.Recent advances in high-throughput technologies have enabled the implementation of personalized cancer therapy for high-risk patients.The use of such high-throughput technologies,including microarray and next generation sequencing,have promoted the discovery of novel targets that offer new treatment strategies for patients lacking other therapeutic options.Many molecular pathways are currently under investigation as therapeutic targets in gastric cancer,including those related to the epidermal growth factor receptor family,the mesenchymal-epithelial transition factor axis,and the phosphatidylinositol 3-kinase-AKTmammalian target of rapamycin factors.Advances in molecular diagnostic tools further support the discovery of new molecular targets.Limitations exist,however;not all patients can be tested for biomarkers,and numerous challenges hamper implementation of targeted therapy in clinical settings.Indeed,the scale of tumor genomic profiling is rapidly outpacing our ability to appropriately synthesize all the information in order to optimally refine patient care.Therefore,clinicians must continue to educate themselves regarding new tools and frameworks,and to utilize multidisciplinary team science,comprised of oncologists,geneticists,pathologists,biologists and bioinformaticians,to successfully implement this genomic approach therapeutically.展开更多
Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb to...Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb toⅢb of HCC treatment.In recent years,immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research.At the same time,targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC,and their clinical application has been quite mature.HCC is the sixth most common malignant tumor in the world.When it comes to its treatment,different therapies have different indications,and their individual efficacies are not satisfactory,which makes the exploration of the use of combination therapy in HCC treatment become a new trend.In this paper,the status of the three therapies and the progress of their combined application are briefly reviewed.展开更多
In recent years,many significant advances have been made on molecular target therapy to aim directly at epidermal growth factor receptors and vascular endothelial growth factor in breast cancers.Clinical studies of su...In recent years,many significant advances have been made on molecular target therapy to aim directly at epidermal growth factor receptors and vascular endothelial growth factor in breast cancers.Clinical studies of such agents as trastuzumab,lapatinib,erlotinib and bevacituzumab have been widely conducted.This paper will review the recent research progress related to targeted therapy.展开更多
The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations ...The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities.The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical outcomes.In this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin B,the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically described.Finally,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.展开更多
Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative researc...Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.展开更多
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 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 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 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.
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.
基金financially supported by Beijing Nova Program(Nos.Z211100002121127 and 20220484219)Beijing Natural Science Foundation(No.L212059)+1 种基金Fundamental Research Funds for the Central Universities(No.3332021101)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-I2M-1-026 and 2021-I2M-1-028).
文摘Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.
基金This study was reviewed and approved by the Ethics Committee of Zhongshan People’s Hospital(Approval No.2022-029).
文摘BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.
文摘Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.
文摘Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal cancer (EC) patients at advanced or metastatic stages. While historically considered incurable, ongoing advancements in medical research have led to the integration of various treatment modalities as primary approaches for managing advanced endometrial cancer. These modalities include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Notably, the introduction of targeted therapy and immunotherapy has significantly enhanced the survival rates of individuals with EC. Immunotherapy has appeared as the predominant treatment for advanced esophageal cancer, while targeted therapy faces certain obstacles. Consequently, this review primarily focuses on the advancements in targeted therapy for esophageal cancer (EC), evaluating the effectiveness and safety of relevant medications, and aiming to provide guidance for the comprehensive management of EC based on current research findings.
文摘Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth of these cells. In the case of gastric cancer,survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently,several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis,prognosis and treatment of gastric tumors.
文摘Gastric cancer is the second leading cause of cancerrelated deaths worldwide.Conventional cytotoxic chemotherapy has limited efficacy for metastatic gastric cancer,with an overall survival of approximately ten months.Recent advances in high-throughput technologies have enabled the implementation of personalized cancer therapy for high-risk patients.The use of such high-throughput technologies,including microarray and next generation sequencing,have promoted the discovery of novel targets that offer new treatment strategies for patients lacking other therapeutic options.Many molecular pathways are currently under investigation as therapeutic targets in gastric cancer,including those related to the epidermal growth factor receptor family,the mesenchymal-epithelial transition factor axis,and the phosphatidylinositol 3-kinase-AKTmammalian target of rapamycin factors.Advances in molecular diagnostic tools further support the discovery of new molecular targets.Limitations exist,however;not all patients can be tested for biomarkers,and numerous challenges hamper implementation of targeted therapy in clinical settings.Indeed,the scale of tumor genomic profiling is rapidly outpacing our ability to appropriately synthesize all the information in order to optimally refine patient care.Therefore,clinicians must continue to educate themselves regarding new tools and frameworks,and to utilize multidisciplinary team science,comprised of oncologists,geneticists,pathologists,biologists and bioinformaticians,to successfully implement this genomic approach therapeutically.
基金supported by National Key Research and Development Program of China Grant under No.2019YFC0118100。
文摘Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb toⅢb of HCC treatment.In recent years,immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research.At the same time,targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC,and their clinical application has been quite mature.HCC is the sixth most common malignant tumor in the world.When it comes to its treatment,different therapies have different indications,and their individual efficacies are not satisfactory,which makes the exploration of the use of combination therapy in HCC treatment become a new trend.In this paper,the status of the three therapies and the progress of their combined application are briefly reviewed.
文摘In recent years,many significant advances have been made on molecular target therapy to aim directly at epidermal growth factor receptors and vascular endothelial growth factor in breast cancers.Clinical studies of such agents as trastuzumab,lapatinib,erlotinib and bevacituzumab have been widely conducted.This paper will review the recent research progress related to targeted therapy.
基金the National Natural Science Foundation of China(Nos.81903662,51903201)China Postdoctoral Science Foundation Grant(Nos.2019M661057,2019M653660)+5 种基金the Applied Basic Research Programs of Shanxi Province(No.201901D211347)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0428)the Startup Foundation for Doctors of Shanxi Province(No.SD1827)Natural Science Foundation of Shaanxi Province(No.2020JQ-086)College Students’Innovation and Entrepreneurship Training Program(No.SJ201910698121)the Startup Foundation for Doctors of Shanxi Medical University(No.XD1824)。
文摘The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities.The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical outcomes.In this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin B,the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically described.Finally,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.
基金This study was supported by funding from the Science Technology and Innovation Committee of Shenzhen Municipality(Grant No.2019N002)Capital's Funds for Health Improvement and Research(Grant No.Z181100001718075).
文摘Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.
