New Molecular Targets in Metastatic Prostate Cancer

Prostate cancer (PCa) is the second leading cause of cancer death in men. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). Over the past decade, increased understanding of the mechanisms that drive resistance to castration has led to the development of next-generation androgen receptor targeting agents such as abiraterone acetate and enzalutamide. Moreover in the last few years, results from large Phase III trials led to the approval of an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T) that showed improvements in terms of overall survival. In the field of metastatic CRPC, other novel therapeutics have recently been proven to extend survival via distinct mechanisms of action such as the new and more potent classes of androgen inhibitors, ortonel, ARN-509 and galeterone, the endothelin A receptor antagonist zibotentan, the Src inhibitor dasatinib, the c-MET inhibitor cabozantinib and the immune checkpoint inhibitor ipilimumab. This review aims to revisit the evolution of androgen receptor targeting therapeutics and to discuss other important alternative biologic pathways that have given rise to new agents in metastatic prostate cancer.

Topical Applications of Thiosulfinate-Enriched Allium sativum Extract Accelerates Acute Cutaneous Wound Healing in Murine Model

Objective To determine whether topical applications of thiosulfinate-enriched Allium sativum extract(TASE)can accelerate acute cutaneous wound healing(WH)in a murine model.Methods Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures.Effects of topical TASE(0.5μg/mL of allicin in 97%ethanol)on acute cutaneous WH were determined in a murine model of acute cutaneous wound.Twelve mice were alternately assigned to the vehicle-and TASE-treated groups(n=6 per group).Expression levels of mRNA for keratinocyte differentiation marker-related proteins(filaggrin,loricrin and involucrin)and lipid synthetic enzymes(elongation of very long chain fatty acids protein 4(ELOVL4),fatty acid synthase(FA2H),3-hydroxy-3-methyl-glutaryl-coenzyme A reductase(HMGCoA),and serine palmitoyltransferase(SPT))were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding,while transepidermal water loss(TEWL)rates were measured in wounded areas.Results TASE accelerated WH both in vivo(40%vs.22%reduction in wound area,P<0.01)and in vitro(90%vs.65%reduction in wound area,P<0.01).Moreover,topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4,HMGCoA,SPT,filaggrin,loricrin and involucrin(P<0.05 vs.vehicle-treated controls)on day 3 after wounding.Likewise,TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8(33.06±2.09 g/(m^2·h)vs.24.60±2.04 g/(m^2·h),P<0.01).Conclusions Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function,leading to acceleration of acute cutaneous WH.Topical products containing TASE could be used to manage acute cutaneous WH.

Is there a place for Ramucirumab after Sorafenib in patients with advanced HCC?

Hepatocellular carcinoma(HCC)is the sixth most commonincident and the fourth most common cause of cancer deathworldwide.It is strongly associated with chronic HepatitisB and C infection and excess alcohol intake(1),makingtreatment of patients with HCC complicated,with the almostuniform presence of concurrent cirrhosis and varying degreesof liver failure,which often fluctuates over time.