Rational design of non-resistant targeted cancer therapies.

ABSTRACT: Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy. Moreover, for these treatment-threatening mutations, the model proposes alternative therapies overcoming the resistance. We exemp

SUBMITTER: Martinez-Jimenez F 

PROVIDER: S-EPMC5402386 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature