Prostate cancer (PCa) remains a major cause of mortality among males in western countries, with little change in mortality rates observed over the past 25 years. Despite recent advances in therapy, treatment options for metastatic castration-resistant disease remain limited. In terms of chemotherapy, only the combination of docetaxel and prednisone has been shown to improve survival in these patients, but duration of response to therapy is short. There is a continuing unmet need for new systemic interventions that act either alone or synergistically with chemotherapy in patients with progressive PCa. Angiogenesis plays a critical role in tumor growth and metastasis in PCa. Several strategies have been used to target angiogenesis; however, it is becoming increasingly apparent that current anti-angiogenic therapies frequently achieve only modest effects in clinical settings. The RhoA/Rho kinase (ROCK) pathway plays a crucial role in the process of angiogenesis in PCa, and studies have demonstrated that ROCK inhibitors decrease VEGF-induced angiogenesis and tumor cell growth. However, further research is required to fully elucidate the molecular mechanisms involved in this pathway, and the potential value of modulating these mechanisms in the treatment of PCa. This study reviews the current understanding of the role of the RhoA/ROCK pathway in the process of angiogenesis in PCa, and the potential of this pathway as a therapeutic target in the future.

Background: Antiplatelet agents are critical for preventing cardiovascular events. However, these therapies are associated with potentially fatal bleeding risks. This study aimed to comprehensively analyze bleeding events associated with antiplatelet therapies over the past two decades and investigate the role of pharmacist-led interventions in mitigating these risks. Methods: Data were extracted from the FDA Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database, both spanning reports from 2004 to 2024. Signal detection was performed using four algorithms: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean. The analysis included temporal trends, indication distribution, time-to-onset, and outcomes of bleeding events. Additionally, the impact of combined drug use on bleeding risk was assessed. The impact of pharmacists in antiplatelet medication management was reviewed, focusing on interventions and their effectiveness in clinical settings. Results: A total of 22 546 bleeding event reports were identified in FAERS and 8916 in JADER. The analysis revealed significant signals for various bleeding adverse events, with the highest signal strength observed for rare events such as hemorrhagic thyroid cyst, spinal subarachnoid hemorrhage, and hemorrhagic adrenal infarction in FAERS, while the three highest signal strengths were Heyde’s syndrome, habitual abortion, and thyroid hemorrhage in JADER. The analysis revealed that older adults aged 65 or older and patients requiring hospitalization were disproportionately affected. The combined use of antiplatelet drugs with non-steroidal anti-inflammatory drugs, anticoagulants, and other drug classes significantly increased bleeding risk. The time-to-onset analysis showed that bleeding events could occur at any time during antiplatelet therapy, highlighting the need for continuous monitoring. Pharmacist-led interventions were reviewed and found to be effective in reducing bleeding complications and improving patient outcomes. Conclusion: This study provides robust evidence of the bleeding risks associated with antiplatelet therapies across diverse clinical settings, emphasizing the need for heightened clinical vigilance. Furthermore, it highlights the critical role of pharmacists in optimizing antiplatelet therapy management and reducing bleeding complications.