To evaluate the influence of rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan allelic discrimination technology. In abiraterone-treated and high-risk patients, rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.
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http://dx.doi.org/10.2217/pgs-2020-0008 | DOI Listing |
Pathologica
October 2024
Division of Experimental Oncology, Istituto Europeo di Oncologia, IRCCS, Milano.
Objective: Prostate cancer (PCa) is the most common cause of cancer-related deaths in men worldwide. BRCA1/2 genes are reported altered in approximately 1% and 8% of PCa cases, respectively. To date, formalin-fixed paraffin-embedded (FFPE) tissues have a consolidate use in the clinical practice, but with a significant drawback related to DNA/RNA degradation during the pre-analytical process.
View Article and Find Full Text PDFEMBO Mol Med
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.
Aggressive prostate cancer (PCa) variants associated with androgen receptor signaling inhibitor (ARSI) resistance and metastasis remain poorly understood. Here, we identify the axon guidance semaphorin receptor PlexinD1 as a crucial driver of cancer aggressiveness in metastatic castration-resistant prostate cancer (CRPC). High PlexinD1 expression in human PCa is correlated with adverse clinical outcomes.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Johns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
Purpose: Prostate-specific membrane antigen (PSMA) radioligand therapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC). Several beta or alpha particle-emitting radionuclide-conjugated small molecules have shown efficacy in late-stage mCRPC and one, [[177Lu]Lu]Lu-PSMA-617, is FDA approved. In addition to tumor upregulation, PSMA is also expressed in kidneys and salivary glands where specific uptake can cause dose-limiting xerostomia and potential for nephrotoxicity.
View Article and Find Full Text PDFHere we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFBackground: In TALAPRO-2, the poly(ADP-ribose) polymerase inhibitor talazoparib plus the androgen receptor-signaling inhibitor enzalutamide improved radiographic progression-free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51-0.
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