Mozihim Azilleo Kristo, Chung Ivy, Said Nur Akmarina B M, Jamil Amira Hajirah Abd
Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
Metabolites. 2022 Apr 14;12(4):350. doi: 10.3390/metabo12040350.
Gynaecological cancers are among the leading causes of cancer-related death among women worldwide. Cancer cells undergo metabolic reprogramming to sustain the production of energy and macromolecules required for cell growth, division and survival. Emerging evidence has provided significant insights into the integral role of fatty acids on tumourigenesis, but the metabolic role of high endogenous oestrogen levels and increased gynaecological cancer risks, notably in obesity, is less understood. This is becoming a renewed research interest, given the recently established association between obesity and incidence of many gynaecological cancers, including breast, ovarian, cervical and endometrial cancers. This review article, hence, comprehensively discusses how FA metabolism is altered in these gynaecological cancers, highlighting the emerging role of oestradiol on the actions of key regulatory enzymes of lipid metabolism, either directly through its classical ER pathways, or indirectly via the IGIFR pathway. Given the dramatic rise in obesity and parallel increase in the prevalence of gynaecological cancers among premenopausal women, further clarifications of the complex mechanisms underpinning gynaecological cancers are needed to inform future prevention efforts. Hence, in our review, we also highlight opportunities where metabolic dependencies can be exploited as viable therapeutic targets for these hormone-responsive cancers.
妇科癌症是全球女性癌症相关死亡的主要原因之一。癌细胞会进行代谢重编程，以维持细胞生长、分裂和存活所需的能量及大分子的产生。新出现的证据为脂肪酸在肿瘤发生中的重要作用提供了重要见解，但高内源性雌激素水平与妇科癌症风险增加之间的代谢作用，尤其是在肥胖人群中，却鲜为人知。鉴于最近肥胖与包括乳腺癌、卵巢癌、宫颈癌和子宫内膜癌在内的许多妇科癌症发病率之间已确立的关联，这正成为一个新的研究热点。因此，这篇综述文章全面讨论了这些妇科癌症中脂肪酸代谢是如何改变的，强调了雌二醇通过其经典的雌激素受体途径直接或通过胰岛素样生长因子受体途径间接对脂质代谢关键调节酶的作用所起的新作用。鉴于肥胖的急剧增加以及绝经前女性妇科癌症患病率的平行上升，需要进一步阐明支撑妇科癌症的复杂机制，为未来的预防工作提供依据。因此，在我们的综述中，我们还强调了将代谢依赖性作为这些激素反应性癌症可行治疗靶点的机会。
