Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
Department of Vascular Surgery, Pius Brinzeu Timisoara City Emergency Clinical Hospital, Timisoara, Romania.
Front Endocrinol (Lausanne). 2021 Jan 21;11:612396. doi: 10.3389/fendo.2020.612396. eCollection 2020.
Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.
目前，依赖性激素的癌症是导致全球癌症相关死亡人数居高不下的主要原因。对这些肿瘤进展背后的分子机制进行研究和阐明是一把双刃剑，它导致了新的治疗选择的扩展和发展，但也带来了触发更具侵袭性、耐药性复发的风险。雄激素、雌激素和孕激素与特定受体（AR、ER、PR）的相互作用已成为乳腺癌、卵巢癌、前列腺癌和子宫内膜癌发生和发展的关键因素。依赖性激素的癌症具有共同的、相当独特的致癌机制，涉及内源性和外源性性激素的积极作用，以维持高有丝分裂率和增加细胞增殖，从而增加异常基因发生和积累的可能性，这些基因与异常细胞分裂和恶性表型的发生高度相关。癌症相关的激素治疗已经发展起来，目前与阻断其他与癌症发生和肿瘤进展相关的信号通路有关，取得了有希望的结果。然而，尽管已经有了既定的发展，但仍有几个缺点需要解决。三萜类化合物是天然存在的次生代谢物，通过各种途径从角鲨烯环化合成。由于其广泛的治疗潜力，包括广泛研究的抗增殖作用，这些化合物无疑是研究和开发新的天然/半合成抗癌疗法的基石。本工作全面描述了三萜类化合物在依赖性激素的癌症中的抗肿瘤活性的研究进展。此外，本综述还强调了各种三萜类化合物的生物活性及其与重要化学结构特征相关的作用机制。
