Department of Gynecological Surgery and Gynecological Oncology, Medical University of Lodz, 4 Kosciuszki Str., 90-419 Lodz, Poland.
Laboratory of Virology, Institute of Medical Biology of the Polish Academy of Sciences, 106 Lodowa Str., 93-232 Lodz, Poland.
Curr Oncol. 2023 Dec 29;31(1):229-249. doi: 10.3390/curroncol31010015.
High-grade serous ovarian cancer (HGSOC) is one of the most lethal tumors generally and the most fatal cancer of the female genital tract. The approved standard therapy consists of surgical cytoreduction and platinum/taxane-based chemotherapy, and of targeted therapy in selected patients. The main therapeutic problem is chemoresistance of recurrent and metastatic HGSOC tumors which results in low survival in the group of FIGO III/IV. Therefore, the prediction and monitoring of chemoresistance seems to be of utmost importance for the improvement of HGSOC management. This type of cancer has genetic heterogeneity with several subtypes being characterized by diverse gene signatures and disturbed peculiar epigenetic regulation. HGSOC develops and metastasizes preferentially in the specific intraperitoneal environment composed mainly of fibroblasts, adipocytes, and immune cells. Different HGSOC subtypes could be sensitive to distinct sets of drugs. Moreover, primary, metastatic, and recurrent tumors are characterized by an individual biology, and thus diverse drug responsibility. Without a precise identification of the tumor and its microenvironment, effective treatment seems to be elusive. This paper reviews tumor-derived genomic, mutational, cellular, and epigenetic biomarkers of HGSOC drug resistance, as well as tumor microenvironment-derived biomarkers of chemoresistance, and discusses their possible use in the novel complex approach to ovarian cancer therapy and monitoring.
高级别浆液性卵巢癌（HGSOC）是最致命的肿瘤之一，也是女性生殖道最致命的癌症。批准的标准治疗包括手术减瘤和基于铂类/紫杉类的化疗，以及在选定患者中进行靶向治疗。主要的治疗问题是复发性和转移性 HGSOC 肿瘤的化疗耐药性，这导致 FIGO III/IV 组的生存率低。因此，预测和监测化疗耐药性对于改善 HGSOC 管理似乎至关重要。这种癌症具有遗传异质性，有几个亚型具有不同的基因特征和失调的特定表观遗传调控。HGSOC 优先在主要由成纤维细胞、脂肪细胞和免疫细胞组成的特定腹腔内环境中发展和转移。不同的 HGSOC 亚型可能对不同的药物敏感。此外，原发性、转移性和复发性肿瘤具有独特的生物学特性，因此对不同的药物有不同的反应。如果不能精确识别肿瘤及其微环境，有效的治疗似乎难以实现。本文综述了 HGSOC 化疗耐药性的肿瘤源性基因组、突变、细胞和表观遗传生物标志物，以及肿瘤微环境来源的化疗耐药性生物标志物，并讨论了它们在卵巢癌治疗和监测的新的复杂方法中的可能应用。
