Structure and energy based quantitative missense variant effect analysis provides insights into drug resistance mechanisms of anaplastic lymphoma kinase mutations.

ABSTRACT: Anaplastic lymphoma kinase (ALK) is considered as a validated molecular target in multiple malignancies, such as non-small cell lung cancer (NSCLC). However, the effectiveness of molecularly targeted therapies using ALK inhibitors is almost universally limited by drug resistance. Drug resistance to molecularly targeted therapies has now become a major obstacle to effective cancer treatment and personalized medicine. It is of particular importance to provide an improved understanding on the mechanisms of resistance of ALK inhibitors, thus rational new therapeutic strategies can be developed to combat resistance. We used state-of-the-art computational approaches to systematically explore the mutational effects of ALK mutations on drug resistance properties. We found the activation of ALK was

SUBMITTER: Li J 

PROVIDER: S-EPMC6045602 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature