Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003...1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003 as a distinct disease entity driven by the fusion of bromodo-main and extraterminal domain(BET)protein 4(BRD4)and NUTM1.In 2004,the World Health Organization(WHO)classified tumors with t(15;19)translocation as a thymic malignancy and designated it“NUT midline carcinoma,”due to its predominant occurrence in midline organs.4 However,subsequent reports revealed NC’s emergence in numerous nonmidline organs,leading to its reclassification as the independent entity“NUT carcinoma of the thorax”by the WHO in 2015.5 NC exhibits rapid progression and profound resistance to conventional radiotherapy and chemotherapy.展开更多
The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage,thus acting as a fortress of the body.However,excessive responses cause detrimen...The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage,thus acting as a fortress of the body.However,excessive responses cause detrimental effects,such as inflammation and autoimmune diseases.To balance the immune responses and maintain immune homeostasis,there are immune checkpoints to terminate overwhelmed immune responses.Pathogens and tumor cells can also exploit immune checkpoint pathways to suppress immune responses,thus escaping immune surveillance.As a consequence,therapeutic antibodies that target immune checkpoints have made great breakthroughs,in particular for cancer treatment.While the overall efficacy of immune checkpoint blockade(ICB)is unsatisfactory since only a small group of patients benefted from ICB treatment.Hence,there is a strong need to search for other targets that improve the efficacy of ICB.Ubiquitination is a highly conserved process which participates in numerous biological activities,including innate and adaptive immunity.A growing body of evidence emphasizes the importance of ubiquitination and its reverse process,deubiquitination,on the regulation of immune responses,providing the rational of simultaneous targeting of immune checkpoints and ubiquitination/deubiquitination pathways to enhance the therapeutic efficacy.Our review will summarize the latest findings of ubiquitination/deubiquitination pathways for anti-tumor immunity,and discuss therapeutic significance of targeting ubiquitination/deubiquitination pathways in the future of immunotherapy.展开更多
The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signa...The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.展开更多
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by the China Postdoctoral Science Foundation(grant number 2022M723207)the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2023KY666)+8 种基金Zhejiang Traditional Chinese Medicine Science Fund Project(grant number 2024ZL372)Qiantang Cross Fund Project(grant number 2023-16)the National Natural Science Foundation of China of Zhejiang Cancer Hospital Cultivation Project(grant number PY2023006)the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2024KY812)the Natural Science Foundation of Zhejiang Province(grant number Q24H160110)the National Natural Science Foundation of China(grant number NSFC82371851)the Science and Technology Foundation of Guizhou Province(Outstanding Young Scientists of Guizhou Province)(grant number Qiankeherencai-YQK(2023)021)the Science and Technology Foundation of Guizhou Province(grant number Qiankehejichu-ZK(2023)General 212)the Science and Technology Foundation of Guizhou Province(grant number Qiankehechengguo-LC(2025)General 068).
文摘1(NUTM1)gene rearrangements(15q14).In 1991,two independent research teams reported NC cases characterized by the t(15;19)translo-cation.1,2 In vitro studies by French et al.3 led to the pivotal discovery of NC in 2003 as a distinct disease entity driven by the fusion of bromodo-main and extraterminal domain(BET)protein 4(BRD4)and NUTM1.In 2004,the World Health Organization(WHO)classified tumors with t(15;19)translocation as a thymic malignancy and designated it“NUT midline carcinoma,”due to its predominant occurrence in midline organs.4 However,subsequent reports revealed NC’s emergence in numerous nonmidline organs,leading to its reclassification as the independent entity“NUT carcinoma of the thorax”by the WHO in 2015.5 NC exhibits rapid progression and profound resistance to conventional radiotherapy and chemotherapy.
基金This work was supported by grants from the National Natural Science Foundation of China(#81802301 to M.Y.,#81770082 to Y.S.,and#81901046 to Y.C.)the Natural Science Foundation of Jiangsu province(#BK20180290 to M.Y.and#BK20170115 to Y.C.).
文摘The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage,thus acting as a fortress of the body.However,excessive responses cause detrimental effects,such as inflammation and autoimmune diseases.To balance the immune responses and maintain immune homeostasis,there are immune checkpoints to terminate overwhelmed immune responses.Pathogens and tumor cells can also exploit immune checkpoint pathways to suppress immune responses,thus escaping immune surveillance.As a consequence,therapeutic antibodies that target immune checkpoints have made great breakthroughs,in particular for cancer treatment.While the overall efficacy of immune checkpoint blockade(ICB)is unsatisfactory since only a small group of patients benefted from ICB treatment.Hence,there is a strong need to search for other targets that improve the efficacy of ICB.Ubiquitination is a highly conserved process which participates in numerous biological activities,including innate and adaptive immunity.A growing body of evidence emphasizes the importance of ubiquitination and its reverse process,deubiquitination,on the regulation of immune responses,providing the rational of simultaneous targeting of immune checkpoints and ubiquitination/deubiquitination pathways to enhance the therapeutic efficacy.Our review will summarize the latest findings of ubiquitination/deubiquitination pathways for anti-tumor immunity,and discuss therapeutic significance of targeting ubiquitination/deubiquitination pathways in the future of immunotherapy.
基金supported by the Natural Science Foundation of China(grant number 82002456)China Postdoctoral Science Foundation(grant number 2022M723207)+10 种基金the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2023KY666)Zhejiang Traditional Chinese Medicine Science Fund Project(grant number 2024ZL372)Qiantang Cross Fund Project(grant number 2023-16)National Natural Science Foundation of China of Zhejiang Cancer Hospital Cultivation Project(grant number PY2023006)the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2024KY812)the Natural Science Foundation of Zhejiang Province(grant number LQ24H160036)Beijing Health Technologies Promotion Program[grant number BHTPP2022041]Peking University Clinical Scientist Training Program and the Fundamental Research Funds for the Central Universities[grant number BMU2024PYJH010]Science Foundation of Peking University Cancer Hospital[grant number PY202333]the Beijing Natural Science Foundation[grant number 7232248]Beijing Hospitals Authority Youth Programme[grant number QML20231902].
文摘The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.
