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) 是美国男性的第二大常见死因。在过去的十年中，PC 的治疗已经发生了转变，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现有疗法在局部 PC 中的应用。在疾病的不同阶段对 PC 的治疗可能包括手术、雄激素剥夺疗法 (ADT)、化学疗法和放射疗法。然而，尽管 ADT 已被证明在 PC 治疗中有效，但其有效性可能是暂时的，因为这些肿瘤经常发展出治疗抗性的分子机制，这使得它们即使在睾酮剥夺、雄激素受体信号传导抑制或细胞毒性的条件下也能存活和增殖药物治疗。重要的，发现 ADT 可诱导关键的改变，这些改变经常导致转移性肿瘤的形成，显示出治疗难治的表型。因此，为了克服这些严重的治疗障碍，正在开发新的 PC 细胞靶向治疗策略。这些包括多种平台，可以增强特定的抗肿瘤药物吸收和增加细胞内的积累。研究表明，由于使用选择性靶向和减少药物剂量，这些新的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是基于选择性配体（与载药纳米颗粒或直接与抗癌药物缀合）与特定质膜生物标志物之间的相互作用，独特地在 PC 细胞表面过表达。另一种靶向治疗方法是提供独特的基于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。本论文回顾了过去 6 年报道的 PC 靶向治疗方式，并讨论了各种靶向治疗策略的优点和局限性。