A view on drug resistance in cancer

Review

关键词: PRIMARY BREAST-CANCER;    CELL LUNG-CANCER;    ACQUIRED-RESISTANCE;    MICROSATELLITE ALTERATIONS;    COMBINATION CHEMOTHERAPY;    MUTATIONAL LANDSCAPE;    CLONAL HEMATOPOIESIS;    CLINICAL RESISTANCE;    ADJUVANT TREATMENT;    NEXT-GENERATION;   

DOI  :  10.1038/s41586-019-1730-1

来源: SCIE

【 摘 要 】

The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy.

【 授权许可】

Free