Amiloride sensitizes prostate cancer cells to the reversible tyrosine kinase inhibitor lapatinib by modulating Erbb3 subcellular localization.

ABSTRACT: Neoadjuvant therapy (NAT) has been studied in clinically localized prostate cancer (PCa) to improve the outcomes from radical prostatectomy (RP) by 'debulking' of high-risk PCa; however, using androgen deprivation therapy (ADT) at this point risks castration resistant PCa (CRPC) clonal proliferation. Our goal is to identify alternative NAT that reduce hormone sensitive PCa (HSPC) without affecting androgen receptor (AR) transcriptional activity. PCa is associated with increased expression and activation of the epidermal growth factor receptor (EGFR) family, including HER2 and ErbB3. The FDA-approved HER2 inhibitor lapatinib has been tested in PCa but was ineffective due to continued activation of ErbB3. We now demonstrate that this is due to ErbB3 being localized to the nucleus in HSPC and

SUBMITTER: Jathal MK 

PROVIDER: S-EPMC11671466 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature