文章：

靶向性类固醇生物合成用于乳腺癌和前列腺癌治疗

Targeting sex steroid biosynthesis for breast and prostate cancer therapy

原文发布日期：2023-09-08

DOI: 10.1038/s41568-023-00609-y

类型: Review Article

开放获取: 否

英文摘要：

Sex steroids, such as androgens and oestrogens, are hormones that primarily regulate the physiology of reproductive organs and maintain reproductive capacity in both men and women, respectively. Later in life, these sex steroids can become major promoters of the growth of cancer in the reproductive tissues, such as the breast and prostate, with breast cancer being the most common cancer in women and prostate cancer being the second most common cancer in men. Oestrogens and androgens act via specific receptor proteins that act as steroid-activated transcription factors. Accordingly, all current endocrine therapies for breast and prostate cancer target steroid–receptor interactions either directly or indirectly. These therapies encompass compounds that inhibit gonadotropin-regulated steroid biosynthesis in the gonads, antagonists and degraders of oestrogen and androgen receptors, and inhibitors of enzymes of oestrogen and androgen biosynthesis. Such enzyme inhibitors can reduce the concentration of potent oestrogens and androgens and their precursors in the tumours by blocking their gonadal and adrenal production, by hindering the activation of the blood-transported precursors within the tumours and/or by inhibiting any local de novo steroid biosynthesis in the tumours. Some well-characterized inhibitors of enzymes of the classical biosynthesis routes of oestrogens and androgens are used in the treatment of breast and prostate cancer, and novel compounds are in development. However, it is likely that not all enzymes involved in sex steroid biosynthesis have been discovered. Furthermore, novel biologically active sex steroids, such as 11-oxygenated androgens, have been more recently identified. Accordingly, so-far-unidentified targets and novel mechanisms for inhibiting sex steroid biosynthesis are expected to provide further tools for more efficient therapies for sex steroid-dependent breast and prostate cancer.

摘要翻译： 

性类固醇（如雄激素和雌激素）是主要调节生殖器官生理、维持男女各自生殖能力的激素。进入生命后期，这些性类固醇可成为乳腺和前列腺等生殖组织癌症生长的主要促进因素；乳腺癌是女性最常见的癌症，前列腺癌在男性中居第二位。雌激素和雄激素通过特异性受体蛋白（作为类固醇激活的转录因子）发挥作用。因此，目前所有针对乳腺癌和前列腺癌的内分泌治疗，均直接或间接靶向类固醇-受体相互作用。这些治疗手段包括：抑制性腺中促性腺激素调控的类固醇生物合成的药物、雌激素和雄激素受体的拮抗剂及降解剂，以及雌激素和雄激素生物合成酶的抑制剂。此类酶抑制剂可通过阻断性腺和肾上腺的激素生成、阻碍血液中运输的前体在肿瘤内活化，和/或抑制肿瘤局部的“从头”类固醇生物合成，从而降低肿瘤内强效雌激素和雄激素及其前体的浓度。一些针对雌激素和雄激素经典生物合成通路的酶抑制剂已用于乳腺癌和前列腺癌的治疗，且新型化合物正在研发中。然而，可能仍有参与性类固醇生物合成的酶尚未被发现；此外，近年还发现了如11-氧代雄激素等新型具有生物活性的性类固醇。因此，迄今未明的靶点及抑制性类固醇生物合成的新机制，有望为性激素依赖的乳腺癌和前列腺癌提供更高效的治疗手段。

原文链接：

Targeting sex steroid biosynthesis for breast and prostate cancer therapy