NF-κB signaling promotes castration-resistant prostate cancer initiation and progression

• Published in: Pharmacology & therapeutics (Oxford) Vol. 211; p. 107538
• Main Authors: Thomas-Jardin, Shayna E., Dahl, Haley, Nawas, Afshan F., Bautista, Monica, Delk, Nikki A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.07.2020
• Subjects: Androgen receptor; Castration resistance; Nuclear factor-κB; Prostate Cancer; CD20; NRD; CD40; RANKL; PCWG2; KLK3; CAPE; IL-1R; LTβR; TNF; LPS; PCa; RHD; BAFF-R; ADT; DHT; NF-κB; NLS; TLR; FKBP51; PHLPP; PSA; CmpdA; BAFF; TNFR; RECIST; IL-1; Castration resistance; AI; IKK; IL-4; CRPCa; DIM; HMG-CoA; IκBα-SR; Nuclear factor-κB; PTHrP; AR; NIK; PIN; DLC1; TAD; Androgen receptor; Prostate Cancer; BPH; NEMO
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2020.107538

Prostate Cancer (PCa) is the second leading cause of cancer-related death in men. Adenocarcinoma of the prostate is primarily composed of Androgen Receptor-positive (AR+) luminal cells that require AR transcriptional activity for survival and proliferation. As a consequence, androgen deprivation and anti-androgens are used to treat PCa patients whose disease progresses following attempted surgical or radiation interventions. Unfortunately, patients with advanced PCa can develop incurable castration-resistant PCa (CRPCa) due to mutated, variant, or overexpressed AR. Conversely, low or no AR accumulation or activity can also underlie castration resistance. Whether CRPCa is due to aberrant AR activity or AR independence, NF-κB signaling is also implicated in the initiation and maintenance of CRPCa and, thus, the NF-κB pathway may be a promising alternative therapeutic target. In this review, we present evidence that NF-κB signaling promotes CRPCa initiation and progression, describe the dichotomic role of NF-κB in the regulation of AR expression and activity and outline studies that explore NF-κB inhibitors as PCa therapies.