BACKGROUND Lung cancer is increasing in incidence worldwide,and targeted therapies are developing at a rapid pace.Furthermore,the KRAS specific gene is strongly associated with non-small cell lung cancer(NSCLC).Adult ...BACKGROUND Lung cancer is increasing in incidence worldwide,and targeted therapies are developing at a rapid pace.Furthermore,the KRAS specific gene is strongly associated with non-small cell lung cancer(NSCLC).Adult patients with locally advanced or metastatic NSCLC who have tested positive for the KRAS G12C mutation and have progressed after at least one systemic treatment are treated with sotorasib.CASE SUMMARY In this study,we report on an advanced NSCLC with a KRAS G12C mutation.The histological diagnosis indicates stage IVB left lung adenocarcinoma with pelvic and bone metastases,identified as cT4N2bM1c.Using circulating tumor DNA analysis,it was possible to determine the mutation abundance of the KRAS gene exon 2,c.34G>Tp.G12C,which was 32.3%.The patient was advised to take sotorasib as part of their treatment.The imaging data were compared before and after treatment.Furthermore,clinical reassessments and regular serial blood testing were conducted.We found that the patient’s clinical symptoms significantly improved after receiving sotorasib medication,and there were no notable side effects,such as liver toxicity,during the treatment.CONCLUSION Sotorasib has shown promising clinical efficacy in patients with the KRAS G12c mutation and has no apparent toxic side effects.展开更多
Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,e...Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,especially the Cys12 mutation in KRAS G12C,have been identified,paving the way for irreversible inhibitor development.A series of clinical trials have proven their efficacies,and the first RAS G12C-targeting drug sotorasib(AMG-510)received approval for non-small cell lung cancer treatment in May,2021.In another approach,the development of indirect RAS inhibitors that target components of the RAS signaling pathway,including the upstream enzyme farnesyl transferase and the downstream effector molecules SOS1,MEK,AKT,and SHP2,has also made significant progress.This review systematically summarizes the latest progress in RAS signaling pathway-targeted drugs,discusses clinical challenges,and proposes beneficial strategies for RAStargeted therapy.展开更多
文摘BACKGROUND Lung cancer is increasing in incidence worldwide,and targeted therapies are developing at a rapid pace.Furthermore,the KRAS specific gene is strongly associated with non-small cell lung cancer(NSCLC).Adult patients with locally advanced or metastatic NSCLC who have tested positive for the KRAS G12C mutation and have progressed after at least one systemic treatment are treated with sotorasib.CASE SUMMARY In this study,we report on an advanced NSCLC with a KRAS G12C mutation.The histological diagnosis indicates stage IVB left lung adenocarcinoma with pelvic and bone metastases,identified as cT4N2bM1c.Using circulating tumor DNA analysis,it was possible to determine the mutation abundance of the KRAS gene exon 2,c.34G>Tp.G12C,which was 32.3%.The patient was advised to take sotorasib as part of their treatment.The imaging data were compared before and after treatment.Furthermore,clinical reassessments and regular serial blood testing were conducted.We found that the patient’s clinical symptoms significantly improved after receiving sotorasib medication,and there were no notable side effects,such as liver toxicity,during the treatment.CONCLUSION Sotorasib has shown promising clinical efficacy in patients with the KRAS G12c mutation and has no apparent toxic side effects.
基金the National Natural Science Foundation of China(No.82173662,81772590 and 81572395)the Natural Science Foundation of Shanghai(No.20ZR1410400)the Extraordinary 2025 Elite Project of Fudan University,the Open Funding of Key Laboratory of Diagnosis and Treatment of Severe Hepato-pancreatic Diseases of Zhejiang Province,and the CAS Interdisciplinary Innovation Team JCTD-2019-07.
文摘Mutated and activated RAS is a key oncogene that drives various human cancers.RAS-targeted therapy has been an extensive research focus but has made little progress given its long history.Several novel binding sites,especially the Cys12 mutation in KRAS G12C,have been identified,paving the way for irreversible inhibitor development.A series of clinical trials have proven their efficacies,and the first RAS G12C-targeting drug sotorasib(AMG-510)received approval for non-small cell lung cancer treatment in May,2021.In another approach,the development of indirect RAS inhibitors that target components of the RAS signaling pathway,including the upstream enzyme farnesyl transferase and the downstream effector molecules SOS1,MEK,AKT,and SHP2,has also made significant progress.This review systematically summarizes the latest progress in RAS signaling pathway-targeted drugs,discusses clinical challenges,and proposes beneficial strategies for RAStargeted therapy.
