Treatment of prostate cancer cell lines with Androgen Receptor and Receptor Tyrosine Kinase inhibitors

Androgen receptor (AR)-targeted therapy is the mainstay of systemic treatments for recurrent and metastastic prostate cancer given the tumor cell's dependency on testosterone signaling for growth and survival. However, numerous bypass pathways have been nominated that may circumvent AR in the context of AR-targeted therapies. In this project, we tested whether AR and receptor tyrosine kinase (RTK) activity opposed each other and if inhibition of one promoted the activation of another. We assessed the impact of AR or RTK inhibition in three prostate cancer cell lines over a 5-day time course. We then performed paired-end RNA-seq to assess differential gene expression. Our findings suggest that the AR and HER2 pathways dynamically interact with each other at the transcriptional level. Differential gene expression in the LAPC-4, LNCaP and 22Rv1 cell lines treated with charcoal-stripped serum (CSS), abiraterone (ABI), enzalutamide (ENZ), afatinib (AFA), dacomitinib (DAC), gefitinib (GEF), lapatinib (LAP), neratinib (NER), sunitinib (SUN), vandetanib (VAN)