液体活检在肺癌管理中新技术的发展和临床应用的拓展

Lung cancer is an exceedingly malignant tumor reported as having the highest morbidity and mortality of any cancer worldwide,thus posing a great threat to global health.Despite the growing demand for precision medicine,current methods for early clinical detection,treatment and prognosis monitoring in lung cancer are hampered by certain bottlenecks.Studies have found that during the formation and development of a tumor,molecular substances carrying tumor-related genetic information can be released into body fluids.Liquid biopsy(LB),a method for detecting these tumor-related markers in body fluids,maybe a way to make progress in these bottlenecks.In recent years,LB technology has undergone rapid advancements.Therefore,this review will provide information on technical updates to LB and its potential clinical applications,evaluate its effectiveness for specific applications,discuss the existing limitations of LB,and present a look forward to possible future clinical applications.Specifically,this paper will introduce technical updates from the prospectives of engineering breakthroughs in the detection of membrane-based LB biomarkers and other improvements in sequencing technology.Additionally,it will summarize the latest applications of liquid biopsy for the early detection,diagnosis,treatment,and prognosis of lung cancer.We will present the interconnectedness of clinical and laboratory issues and the interplay of technology and application in LB today.

RANBP9 as potential therapeutic target in non-small cell lung cancer

Non-small cell lung cancer(NSCLC)remains the leading cause of cancer-related deaths in the Western world.Despite progress made with targeted therapies and immune checkpoint inhibitors,the vast majority of patients have to undergo chemotherapy with platinum-based drugs.To increase efficacy and reduce potential side effects,a more comprehensive understanding of the mechanisms of the DNA damage response(DDR)is required.We have shown that overexpressby live cell imaging Incuyion of the scaffold protein RAN binding protein 9(RANBP9)is pervasive in NSCLC.More importantly,patients with higher levels of RANBP9 exhibit a worse outcome from treatment with platinum-based drugs.Mechanistically,RANBP9 exists as a target and an enabler of the ataxia telangiectasia mutated(ATM)kinase signaling.Indeed,the depletion of RANBP9 in NSCLC cells abates ATM activation and its downstream targets such as pby live cell imaging Incuy53 signaling.RANBP9 knockout cells are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related(ATR)kinase but not to ATM inhibition.The absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-Polymerase(PARP)resulting in a“BRCAness-like”phenotype.In summary,as a result of increased sensitivity to DNA damaging drugs conferred by its ablation in vitro and in vivo,RANBP9 may be considered as a potential target for the treatment of NSCLC.This article aims to report the results from past and ongoing investigations focused on the role of RANBP9 in the response to DNA damage,particularly in the context of NSCLC.This review concludes with future directions and speculative remarks which will need to be addressed in the coming years.