Journal
NATURE
Volume 575, Issue 7782, Pages 299-309Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-019-1730-1
Keywords
-
Categories
Funding
- [T32 CA009207]
- [R01 CA207244]
- [P30 CA008748]
- [R01 CA190642-01A1]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available