Can THEM6 targeting stop resistance to prostate cancer treatment?

Abstract

Prostate cancer (PCa) clinical management relies heavily on androgen-deprivation therapy (ADT). However, despite experiencing initial clinical benefit, patients getting ADT for non-resectable PCa eventually relapse and develop fatal castration-resistant PCa (CRPC). Multiple mechanisms of acquired resistance to treatment have been reported, including metabolic adaptation (Marine etal, 2020). Notably, activation of the endoplasmic reticulum (ER) unfolded protein response (UPR) has been associated with oncogenic transformation (Hart etal, 2012), tumor progression, metastasis dissemination, and resistance to therapy (Chen & Cubillos-Ruiz, 2021). Targeting different branches of ER UPR has been found to be an effective tool against aggressive PCa (Nguyen etal, 2018; Sheng etal, 2019). Therefore, a better understanding of these pathways may lead to the identification of novel drug targets.