Bromocriptine monotherapy overcomes prostate cancer chemoresistance in preclinical models.

Chemoresistance is a major obstacle in the clinical management of metastatic, castration-resistant prostate cancer (PCa). It is imperative to develop novel strategies to overcome chemoresistance and improve clinical outcomes in patients who have failed chemotherapy. Using a two-tier phenotypic screening platform, we identified bromocriptine mesylate as a potent and selective inhibitor of chemoresistant PCa cells.

Novel roles for HMGA2 isoforms in regulating oxidative stress and sensitizing to RSL3-Induced ferroptosis in prostate cancer cells.

Oxidative stress is increased in several cancers including prostate cancer, and is currently being exploited in cancer therapy to induce ferroptosis, a novel nonapoptotic form of cell death. High mobility group A2 (HMGA2), a non-histone protein up-regulated in several cancers, can be truncated due to chromosomal rearrangement or alternative splicing of HMGA2 gene. The purpose of this study is to investigate the role of wild-type vs.

Black in Cancer: Two Years of Empowering the Next Generation.

In the 2 years since the inception of Black in Cancer, we have modeled an action-oriented commitment to improving Black representation across all levels of the cancer spectrum. We reflect on our successes and consider new ways to innovate and inspire the cancer community.

Serum deprivation initiates adaptation and survival to oxidative stress in prostate cancer cells.

Inadequate nutrient intake leads to oxidative stress disrupting homeostasis, activating signaling, and altering metabolism. Oxidative stress serves as a hallmark in developing prostate lesions, and an aggressive cancer phenotype activating mechanisms allowing cancer cells to adapt and survive. It is unclear how adaptation and survival are facilitated; however, literature across several organisms demonstrates that a reversible cellular growth arrest and the transcription factor, nuclear factor-kappaB (NF-κB), contribute to cancer cell survival and therapeutic resistance under oxidative stress.

Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration.

G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential However, the reduced signaling entities responsible for the observed functional outputs remain elusive. This study now delineates the signaling mechanism whereby heterodimeric association between CXCR4 and CB2, induced by simultaneous agonist treatment, results in decreased CXCR4-mediated cell migration, invasion, and adhesion through inhibition of the Gα13/RhoA signaling axis.