Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer.

ABSTRACT: Drug resistance remains an elusive problem in cancer therapy, particularly for novel targeted therapies. Much work is focused upon the development of an arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops over time. Currently, after failure of first line ALK TKI therapy, another ALK TKI is administered, though collateral sensitivity is not considered. To address this, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK TKIs, and performed a collateral sensitivity analysis. All ALK inhibitor resistant cell lines displayed significant cross-resistance to all other ALK inhibitors. We then evaluated ALK-inhibitor sensitivities after drug holidays of varying length

SUBMITTER: Dhawan A 

PROVIDER: S-EPMC5430816 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature