Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

Abstract

High-grade serous tubo-ovarian cancer (HGSTOC) is the most lethal tumor of the female genital tract. The foregoing therapy consists of cytoreduction followed by standard platinum/taxane chemotherapy; alternatively, for primary unresectable tumors, neo-adjuvant platinum/taxane chemotherapy followed by delayed interval cytoreduction. In patients with suboptimal surgery or advanced disease, different forms of targeted therapy have been accepted or tested in clinical trials. Studies on HGSTOC discovered its genetic and proteomic heterogeneity, epigenetic regulation, and the role of the tumor microenvironment. These findings turned attention to the fact that there are several distinct primary tumor subtypes of HGSTOC and the unique biology of primary, metastatic, and recurrent tumors may result in a differential drug response. This results in both chemo-refractoriness of some primary tumors and, what is significantly more frequent and destructive, secondary chemo-resistance of metastatic and recurrent HGSTOC tumors. Treatment possibilities for platinum-resistant disease include several chemotherapeutics with moderate activity and different targeted drugs with difficult tolerable effects. Therefore, the question appears as to why different subtypes of ovarian cancer are predominantly treated based on the same therapeutic schemes and not in an individualized way, adjusted to the biology of a specific tumor subtype and temporal moment of the disease. The paper reviews the genomic, mutational, and epigenetic signatures of HGSTOC subtypes and the tumor microenvironment. The clinical trials on personalized therapy and the overall results of a new, comprehensive approach to personalized therapy for ovarian cancer have been presented and discussed.

Paradigm Shift: A Comprehensive Review of Ovarian Cancer Management in an Era of Advancements

“…For instance, those with early disease stages, type I tumours and lower baseline CA-125 levels usually have higher survival [12,[83][84][85][86][87][88]. However, ongoing research has recently identified several molecular biomarkers associated with OC treatment response and prognosis, including mutations, gene expression patterns, and/or epigenetic changes [89][90][91]. This is particularly relevant given the high heterogeneity that characterises HGSC, with the predominant and most lethal OC subtype accounting for 70% of OC-related deaths [92].…”

“…Since the proposal of these models, the integrative analysis of tumour (epi)genetic and molecular signatures has more or less confirmed the existence of these four HGSC subtypes with an impact on prognosis and/or treatment response (Table 1). This is anticipated to change OC management by facilitating personalised treatment [91]. Abbreviations: HRR, homologous recombination repair; NGS, next-generation sequencing; PFS, progression-free survival; TCGA, The Cancer Genome Atlas.…”

“…Despite their potential, the high heterogeneity of ovarian tumours and drug resistance are significant obstacles to the implementation of these drugs [226][227][228][229]. Nevertheless, progress in disease (epi)genetic and molecular profiling may help solve some of the current issues [91].…”