New insights for drug resistance in metastatic castration-resistant prostate cancer

Abstract

Prostate cancer is the most common cancer and is the second leading cause of cancer-related deaths among men in the United States. Androgen deprivation therapy (ADT) is the standard treatment for advanced-stage prostate cancer; however, this treatment eventually fails, leading to an incurable disease subtype known as metastatic castration-resistant prostate cancer (mCRPC). There are several molecular mechanisms that facilitate the development of mCRPC engaging androgen receptor (AR) growth axis, including AR amplification, gain of function AR mutations, and AR splice variants that are constitutively active and are a foremost factor for mCRPC development. AR-independent mechanisms with exceptionally low or absent AR expression found in cancer cells suppress ADT effectiveness and contribute to aggressive variants, including neuroendocrine differentiation. Several other AR regulatory factors such as epigenetic modification(s), and DNA damage response have been reported during post-ADT exposure and play a crucial role in mCRPC development. Therefore, targeting prostate cancer cells before their progression to mCRPC would improve patient outcomes. This special issue in “Cancer Drug Resistance” focuses on understanding the mechanism(s) and development of mCRPC resistance. This special issue also highlights the therapeutic strategies to combat against resistant subtype. This issue comprehensively reviews the mCRPC and delivers the update in the forum of mCRPC resistance development.

Pseudo-grading of tumor subpopulations from single-cell transcriptomic data using Phenotype Algebra

“…h, i). This is in line with the hypothesis that prolonged exposure to ATTs can give rise to aggressive subtypes in response to treatment [85][86][87] . The expression pattern of a gene set of 'efflux transmembrane transporters' matched most closely Kendall's tau 0.93) the predicted risk ranking of the clusters (Fig.…”

β-Arrestin2 promotes docetaxel resistance of castration-resistant prostate cancer via promoting hnRNP A1-mediated PKM2 alternative splicing

“…Despite significant improvements in the treatment of prostate cancer (PCa), patients with advanced disease will ultimately progress to metastatic castration-resistant prostate cancer (mCRPC) [ 1 , 3 ]. While various drugs, including docetaxel (DTX), the first-line therapy for mCRPC, initially lead to disease regression, resistance to these drugs ultimately renders mCRPC incurable [ 2 , 4 ]. Therefore, understanding the mechanisms of drug resistance and identifying new therapeutic targets remain crucial in delaying or reversing the progression of CRPC.β-arrestins, including β-arrestin1 and β-arrestin2, are identified as negative regulators of G-protein-coupled receptor (GPCR) signaling in initial.…”

“…Docetaxel (DTX) has been the mainstay of chemotherapy for PCa and is the first drug to improve overall survival in CRPC patients. However, most patients treated with DTX eventually resist the drug, leading to refractory disease and disease recrudescence [ 2 – 4 ]. Therefore, it remains a significant challenge to identify the underlying mechanisms of DTX resistance and improve clinical outcomes for patients with CRPC.β-arrestin2 is a negative regulator of G-protein-coupled receptor (GPCR) signaling and plays an important role in cancer progression by serving as an adaptor to guide distinct pathway signals [ 5 , 6 ].…”

Knowledge structure and emerging trends of AR variants in prostate cancer: a bibliometric analysis based on CiteSpace and VOSviewer

“…Most PCa progress to the castration-resistance stage with androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors [3]. Patients of this cancer stage develop primary or secondary resistance to androgen-or androgen receptor-targeted agents which are associated with multiple underlying mechanisms [4][5][6][7]. It is also reported that incidence of PCa is associated with germline mutations and polymorphisms of AR gene [8].…”