National Cancer Institute 5R01CA299202-02

Targeting FOXA2/AP-1 axis to overcome lineage plasticity and therapy resistance in castration-resistant prostate cancer

This award funds research to understand and target the FOXA2-AP-1 axis in prostate cancer to overcome therapy resistance caused by lineage plasticity.

Description

Prostate tumor cells can escape from androgen receptor-targeted therapies by changing their cell identity, a process called lineage plasticity; however, the mechanism by which tumor cells initiate this progression is poorly understood. From preliminary studies, we have found that FOXA2, a lineage-specific pioneer transcription factor, can function to initiate a multilineage transition state by collaborating and reprogramming AP-1 transcription factors. The goal of this project is to elucidate how this FOXA2-AP-1 axis contributes to the initiation and determination of cellular identity shifts in prostate cancer cells and develop a combination therapy to target this axis to reduce tumor lineage plasticity and overcome resistance to androgen receptor-targeted therapies.

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