Platinum is the backbone of systemic treatment in ovarian cancer and development of platinum resistance is associated with poor survival. Here, we perform a comprehensive review of the literature regarding resistance mechanisms and advances in therapy for platinum resistant ovarian cancer, with a focus on high-grade serous carcinoma. Platinum resistance can be intrinsic or acquired. Resistance mechanisms are complex and diverse. Intracellular mechanisms include restoration of homologous recombination repair, reduced intracellular accumulation of platinum, blocked cellular replication and inhibition of apoptosis. These act in concert with immunosuppressive, angiogenic and stromal changes in the tumour microenvironment to drive treatment resistance. Current molecular stratification lacks prognostic and predictive validity, limited in part by the extreme genomic complexity of high-grade serous ovarian cancer. Clinical trials represent an important option for patients as standard of care treatment options have limited efficacy. The most promising trials appear to focus on rational combinations of chemotherapy, immunotherapy, anti-angiogenics, PARP inhibitors, targeted therapy and/or antibody-drug conjugates. Resistance mechanisms are multifactorial with capacity to evolve over time, making clinical detection challenging. It is increasingly apparent that clinical trials must incorporate correlative studies to elucidate predictive biomarkers. They must also adopt endpoints that can appropriately measure benefit for palliative treatments. Future research must aim to deepen our understanding of the biology of this disease, and deliver meaningful benefit in terms of improved quality of life and overall survival for women with platinum resistant ovarian cancer.

铂是卵巢癌全身治疗的支柱，铂耐药性的发展与较差的生存率有关。在这里，我们对有关铂耐药性卵巢癌的耐药机制和治疗进展的文献进行全面回顾，重点关注高级别浆液性癌。铂电阻可以是固有的或后天的。耐药机制复杂多样。细胞内机制包括同源重组修复的恢复、铂的细胞内积累减少、细胞复制受阻和细胞凋亡的抑制。这些与肿瘤微环境中的免疫抑制、血管生成和基质变化协同作用，以驱动治疗耐药性。目前的分子分层缺乏预后和预测有效性，部分受限于高级别浆液性卵巢癌的极端基因组复杂性。临床试验代表了患者的重要选择，因为标准护理治疗方案的疗效有限。最有希望的试验似乎集中在化学疗法、免疫疗法、抗血管生成剂、PARP 抑制剂、靶向疗法和/或抗体药物偶联物的合理组合上。耐药机制是多因素的，具有随时间演变的能力，使临床检测具有挑战性。越来越明显的是，临床试验必须结合相关研究来阐明预测性生物标志物。他们还必须采用可以适当衡量姑息治疗益处的终点。未来的研究必须旨在加深我们对这种疾病生物学的理解，