Medical Oncology Division of Urogenital and Head and Neck Tumours, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy.
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, 60126 Ancona, Italy.
Cells. 2020 Jun 22;9(6):1522. doi: 10.3390/cells9061522.
Medical treatment for metastatic castration-resistant prostate cancer (mCRPC) patients has progressively been evolving from a nonspecific clinical approach to genomics-oriented therapies. The scientific community is in fact increasingly focusing on developing DNA damage repair (DDR) defect-driven novel molecules, both as single-agent therapy and in combined treatment strategies. Accordingly, research is under way into combined drug therapies targeting different pathways, e.g. androgen receptor signaling (ARS) and poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes, immune checkpoint (IC) and PARP, IC, and ARS, and prostate-specific membrane antigen (PSMA). In an attempt to formulate evolving treatment paradigms in mCRPC patients, here we selected clinical research into patients undergoing therapies with emerging molecules, with particular emphasis towards PARP-, IC-, and PSMA-inhibitors. In order to focus on those molecules and drug combinations most likely to be translated into routine clinical care in the near future, we selected only those clinical studies currently recruiting patients. A PubMed search focusing on the keywords "prostate cancer", "metastatic castration-resistant prostate cancer", "DDR pathways", "ARS inhibitors", "PARP inhibitors", "IC inhibitors", "PSMA-targeting agents", and "drug combinations" was performed.
转移性去势抵抗性前列腺癌 (mCRPC) 患者的治疗方法已逐渐从非特异性临床方法发展为基于基因组学的治疗方法。事实上，科学界越来越关注开发 DNA 损伤修复 (DDR) 缺陷驱动的新型分子，无论是作为单一药物治疗还是联合治疗策略。因此，正在研究针对不同途径的联合药物治疗，例如雄激素受体信号 (ARS) 和聚 (二磷酸腺苷 [ADP]-核糖) 聚合酶 (PARP) 酶、免疫检查点 (IC) 和 PARP、IC 和 ARS 以及前列腺特异性膜抗原 (PSMA)。为了制定 mCRPC 患者不断发展的治疗模式，我们在这里选择了对接受新兴分子治疗的患者进行的临床研究，特别强调了 PARP、IC 和 PSMA 抑制剂。为了关注那些最有可能在不久的将来转化为常规临床护理的分子和药物组合，我们仅选择了那些目前正在招募患者的临床研究。进行了一项以“前列腺癌”、“转移性去势抵抗性前列腺癌”、“DDR 途径”、“ARS 抑制剂”、“PARP 抑制剂”、“IC 抑制剂”、“PSMA 靶向药物”和“药物组合”为关键词的 PubMed 搜索。
