Kindlon Erin A, Pidgeon Graham P
Translational Oncology, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin D02PN40, Ireland.
Department of Surgery, Trinity Cancer Institute, St James's Hospital & Trinity College Dublin, Dublin D08W9RT, Ireland.
Acad Oncol. 2025;2(2). doi: 10.20935/acadonco7784. Epub 2025 Jun 24.
Ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death worldwide. It is an aggressive disease with five-year survival rates below 45% and many patients relapse within 2 years. Further treatments become more intense, resulting in chemotherapy drug resistance and increased toxicity. This has created the need to develop new therapeutic strategies to improve the quality of life and treatment options for ovarian cancer patients. Studies have reported the role of cysteine in ovarian cancer, primarily as a precursor of glutathione (GSH), contributing to the endogenous antioxidant mechanism. The membrane-permeable cysteine precursor N-acetylcysteine (NAC) can enhance the intracellular cysteine pool and thus results in decreased oxidative stress. This characteristic provides NAC with a rationale as a potentially effective chemo-protectant in ovarian cancer treatment. In this review, we summarize the effects of NAC supplementation in ovarian cancer from recent preclinical studies. The role of NAC in chemotherapy response, and mechanisms to overcome chemo resistance in ovarian cancer (including targeting the Mirk/dyrk1B kinase pathway) are also explored. While NAC holds therapeutic promise in alleviating treatment-associated toxicities, its application in ovarian cancer requires careful consideration based on tumour subtype, redox context, and treatment timing. Future research incorporating subtype-specific models and clinical trials will be essential to delineate the precise role of NAC and optimize its integration into ovarian cancer treatment regimens.
卵巢癌是女性中第七大常见癌症,也是全球第八大常见癌症死亡原因。它是一种侵袭性疾病,五年生存率低于45%,许多患者在两年内复发。进一步的治疗会变得更加激烈,导致化疗药物耐药性和毒性增加。这就产生了开发新治疗策略以改善卵巢癌患者生活质量和治疗选择的需求。研究报告了半胱氨酸在卵巢癌中的作用,主要作为谷胱甘肽(GSH)的前体,有助于内源性抗氧化机制。膜通透性半胱氨酸前体N-乙酰半胱氨酸(NAC)可以增强细胞内半胱氨酸池,从而降低氧化应激。这一特性为NAC作为卵巢癌治疗中潜在有效的化学保护剂提供了理论依据。在本综述中,我们总结了近期临床前研究中补充NAC对卵巢癌的影响。还探讨了NAC在化疗反应中的作用以及克服卵巢癌化疗耐药性的机制(包括靶向Mirk/dyrk1B激酶途径)。虽然NAC在减轻治疗相关毒性方面具有治疗前景,但其在卵巢癌中的应用需要根据肿瘤亚型、氧化还原背景和治疗时机进行仔细考虑。纳入亚型特异性模型和临床试验的未来研究对于阐明NAC的确切作用并优化其纳入卵巢癌治疗方案至关重要。