Abstract
Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.
Highlights
The overexpression of miR-30d and miR-323 were described to increase vascular endotheendothelial growth factortransforming (VEGF) synthesis and secretion by Prostate cancer (PC) cells and, enhance VEGF-mediated angiogenesis in PC [88]. miR-296 controls the levels of VEGF and platelet-derived growth factor (PDGF) receptors in angiogenic endothelial cells, while miR-21 and miR-182 regulates the activation of Hypoxia-Inducible Factors (HIF)-1α and HIF-1α-moderated angiogenesis [89]
Multiple clinical trials utilizing antiangiogenic treatment pathways have resulted in discouraging outcomes; anti-angiogenic treatment is still promising and calls for future evaluation in metastatic castration-resistant PC (mCRPC)
Markers used to assess treatment response (PFS, prostate-specific antigen (PSA) response) might not be suitable for assessing activity of angiogenesis inhibitors calling for more research in this setting
Summary
Patients are stratified into low, intermediate and high risk, based on the sum of Gleason patterns, prostate-specific antigen (PSA) level and clinical stage [9,10,11]. FDA-approved cancer vaccine in the United States, increasing median OS by 4.1 months compared with placebo This therapy is recommended for patients who are asymptomatic or minimally symptomatic and when their PSA levels are low [22]. Cabazitaxel represents a tubulin-binding taxane, which increased median OS by 2.4 months compared with mitoxantrone [20] Radioligand therapies, such as lutetium-177 (177 Lu)–PSMA-617 can target PC cells, while sparing most normal tissues in patients selected with imaging.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
