The Laboratory of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
The Laboratory of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
Drug Resist Updat. 2021 May;56:100762. doi: 10.1016/j.drup.2021.100762. Epub 2021 Mar 19.
Prostate cancer (PC) is the second most common cause of death amongst men in the USA. Therapy of PC has been transformed in the past decade by introducing novel therapeutics, advanced functional imaging and diagnostic approaches, next generation sequencing, as well as improved application of existing therapies in localized PC. Treatment of PC at the different stages of the disease may include surgery, androgen deprivation therapy (ADT), chemotherapy and radiation therapy. However, although ADT has proven efficacious in PC treatment, its effectiveness may be temporary, as these tumors frequently develop molecular mechanisms of therapy resistance, which allow them to survive and proliferate even under conditions of testosterone deprivation, inhibition of androgen receptor signaling, or cytotoxic drug treatment. Importantly, ADT was found to induce key alterations which frequently result in the formation of metastatic tumors displaying a therapy refractory phenotype. Hence, to overcome these serious therapeutic impediments, novel PC cell-targeted therapeutic strategies are being developed. These include diverse platforms enabling specific enhanced antitumor drug uptake and increased intracellular accumulation. Studies have shown that these novel treatment modalities lead to enhanced antitumor activity and diminished systemic toxicity due to the use of selective targeting and decreased drug doses. The underlying mechanism of targeting and internalization is based upon the interaction between a selective ligand, conjugated to a drug-loaded nanoparticle or directly to an anti-cancer drug, and a specific plasma membrane biomarker, uniquely overexpressed on the surface of PC cells. Another targeted therapeutic approach is the delivery of unique anti-oncogenic signaling pathway-based therapeutic drugs, which are selectively cytotoxic to PC cells. The current paper reviews PC targeted modalities reported in the past 6 years, and discusses both the advantages and limitations of the various targeted treatment strategies.
前列腺癌（PC）是美国男性第二大常见死因。在过去的十年中，通过引入新的治疗方法、先进的功能成像和诊断方法、下一代测序以及改进局部 PC 中现有治疗方法的应用，PC 的治疗发生了转变。在疾病的不同阶段，PC 的治疗可能包括手术、雄激素剥夺疗法（ADT）、化疗和放射治疗。然而，尽管 ADT 已被证明在 PC 治疗中有效，但它的有效性可能是暂时的，因为这些肿瘤经常发展出治疗耐药的分子机制，即使在睾酮剥夺、雄激素受体信号抑制或细胞毒性药物治疗的情况下，这些机制也允许它们存活和增殖。重要的是，已经发现 ADT 诱导了经常导致形成具有治疗抵抗表型的转移性肿瘤的关键改变。因此，为了克服这些严重的治疗障碍，正在开发针对 PC 细胞的新型治疗策略。这些策略包括各种平台，能够特异性增强抗肿瘤药物摄取和增加细胞内积累。研究表明，由于使用了选择性靶向和减少药物剂量，这些新型治疗方式可提高抗肿瘤活性并降低全身毒性。靶向和内化的潜在机制基于选择性配体与载药纳米颗粒或直接与抗癌药物的相互作用，以及在 PC 细胞表面独特过表达的特定质膜生物标志物。另一种靶向治疗方法是递送基于独特抗肿瘤信号通路的治疗药物，这些药物对 PC 细胞具有选择性细胞毒性。本文综述了过去 6 年中报道的针对 PC 的靶向模式，并讨论了各种靶向治疗策略的优缺点。
