Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.
Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.
Life Sci. 2020 Oct 15;259:118208. doi: 10.1016/j.lfs.2020.118208. Epub 2020 Aug 4.
Cancer is the second leading cause of death worldwide, with prostate cancer, the second most commonly diagnosed cancer among men. Prostate cancer develops in the peripheral zone of the prostate gland, and the initial progression largely depends on androgens, the male reproductive hormone that regulates the growth and development of the prostate gland and testis. The currently available treatments for androgen dependent prostate cancer are, however, effective for a limited period, where the patients show disease relapse, and develop androgen-independent prostate cancer (AIPC). Studies have shown various intricate cellular processes such as, deregulation in multiple biochemical and signaling pathways, intra-tumoral androgen synthesis; AR over-expression and mutations and AR activation via alternative growth pathways are involved in progression of AIPC. The currently approved treatment strategies target a single cellular protein or pathway, where the cells slowly develop resistance and adapt to proliferate via other cellular pathways over a period of time. Therefore, an increased research aims to understand the efficacy of combination therapy, which targets multiple interlinked pathways responsible for acquisition of resistance and survival. The combination therapy is also shown to enhance efficacy as well as reduce toxicity of the drugs. Thus, the present review focuses on the signaling pathways involved in the progression of AIPC, comprising a heterogeneous population of cells and the advantages of combination therapy. Several clinical and pre-clinical studies on a variety of combination treatments have shown beneficial outcomes, yet further research is needed to understand the potential of combination therapy and its diverse strategies.
癌症是全球第二大致死原因，前列腺癌是男性中第二大常见的癌症。前列腺癌发生在前列腺的外周带，其初始进展在很大程度上依赖于雄激素，雄激素是一种调节前列腺和睾丸生长发育的男性生殖激素。然而，目前用于治疗雄激素依赖性前列腺癌的方法在有效时间有限后，患者会出现疾病复发，并发展为雄激素非依赖性前列腺癌（AIPC）。研究表明，各种复杂的细胞过程，如多个生化和信号通路的失调、肿瘤内雄激素合成、AR 过度表达和突变以及通过替代生长途径激活 AR，都与 AIPC 的进展有关。目前批准的治疗策略针对单个细胞蛋白或途径，随着时间的推移，细胞会逐渐产生耐药性，并通过其他细胞途径增殖来适应。因此，越来越多的研究旨在了解联合治疗的效果，这种治疗方法针对的是导致耐药性和生存的多个相互关联的途径。联合治疗还显示出增强疗效和降低药物毒性的作用。因此，本综述重点介绍了参与 AIPC 进展的信号通路，包括异质细胞群和联合治疗的优势。多项关于各种联合治疗的临床和临床前研究表明，联合治疗具有有益的效果，但仍需要进一步研究以了解联合治疗的潜力及其多样化的策略。
