Drug resistance has limited the efficacy of almost all targeted therapeutic agents used to treat cancers. Although some of the most successful anti-cancer drugs to emerge in the last 2 decades are kinase inhibitors, they are invariably associated with relapse due to development of resistance during the course of treatment. In this project, we will derive and characterize drug resistant clones to delineate mechanisms of acquired resistance to kinase inhibitors. This research work has the potential to reveal clinically relevant drug resistance mechanisms for some of the widely used anti-cancer agents. These resistance mechanisms could be targeted to achieve durable responses to cancer therapy.

Aim: Delineating mechanisms of acquired resistance to kinase inhibitors

Hypothesis: Unbiased investigation of drug resistant cancer cells by employing genomic, transcriptomic and proteomic methods can reveal clinically relevant mechanisms of acquired drug resistance to small molecule kinase inhibitors used in cancer treatment.

Approaches

1)  Generate drug resistant derivatives of cancer cell lines by subjecting them to selection pressure under targeted kinase inhibitors that are in clinical use

2) Genomic, transcriptomic, proteomic and phosphoproteomic characterization of drug resistant clones

3)   Determine molecular basis of acquired resistance by integrating multi-omics data

4)  Determine novel therapeutic intervention strategies to target acquired drug resistance

Supervisor

A/Prof Harsha Gowda

Group leader
QIMR Berghofer
Adjunct Associate Professor
Faculty of Medicine