Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, London Health Sciences Centre, Western University, London, ON N6A 5W9, Canada.
Juravinski Cancer Centre, McMaster University, Hamilton, ON L8V 5C2, Canada.
Curr Oncol. 2022 Jul 18;29(7):5054-5076. doi: 10.3390/curroncol29070400.
Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy.
前列腺癌仍然是全球男性癌症死亡的主要原因之一。在过去的十年中,已经批准了几种治疗晚期前列腺癌的新方法。由于有多种可用的药物,包括细胞毒性药物、雄激素受体轴靶向治疗和α发射辐射治疗,确定其最佳顺序仍然是一个挑战。对前列腺癌生物学的认识进展为更精细和个性化的治疗选择过程提供了机会。随着分子测序技术的进步,通过鉴定潜在的治疗靶点和预测性生物标志物进行基因组精确性的进展正在迅速发展。在这篇综述中,我们讨论了用于治疗晚期前列腺癌的生物标志物驱动的治疗方法。首先,我们介绍了用于治疗晚期疾病的既定全球标准治疗方法(如化疗和雄激素受体轴靶向药物)的预测性生物标志物。我们还讨论了最近为特殊人群批准的靶向药物,例如聚 ADP 核糖聚合酶(PARP)抑制剂在转移性去势抵抗性前列腺癌且同源重组修复缺陷肿瘤患者中,pembrolizumab 在高水平微卫星不稳定或高肿瘤突变负担的患者中,以及针对表达 PSMA 的肿瘤的 PSMA 定向放射性配体治疗。此外,我们还讨论了不断发展的治疗方法,例如癌症疫苗、嵌合抗原受体 T 细胞(CAR-T)、双特异性 T 细胞衔接器(BiTE)、其他靶向药物如 AKT 抑制剂以及各种联合治疗。总之,分子遗传学的进步已经开始推动晚期前列腺癌管理中的个性化医学向前发展,允许更精确、基于生物标志物的治疗选择,目标是提高整体疗效。