Multi‐omics in high‐grade serous ovarian cancer: Biomarkers from genome to the immunome

Abstract

Epithelial ovarian cancer (EOC) is a lethal gynaecological disease that imposes significant burden on health care and patient quality of life. High-grade serous carcinoma of the ovary (HGSC) is the most prevalent histological type of EOC. A vast majority of HGSC cases are diagnosed at late stages of the disease, limiting the opportunity for clinical intervention and resulting in a 10-year survival rate of <20%. Recent innovations in high-throughput molecular analysis of patient-derived specimens may address these clinical challenges by providing an enhanced understanding of the molecular aetiology of ovarian cancer, in addition to offering several opportunities for rational biomarker and targeted therapy discovery. In this review, we highlight the most significant contributions of omics approaches and how the advent of immunomics can aid in personalized combination chemo-immunotherapy in ovarian cancer treatment. We further provide insights into immunogenomic correlates of pre-treatment tumour immune microenvironment and some of the potential interpretations of immunomic data that require further validation, based on stromal and immune contributions to biomarker signatures. We believe a comprehensive integrative approach via meta-analysis of large ovarian cancer molecular profiling data sets is urgently needed to define robust prognostic and predictive classifiers of disease progression and treatment response. These investigations will inform rationalized biomarker-driven combination chemo-immunotherapy trials for improving response and survival of ovarian cancer patients.

Identification of AK4 as a novel therapeutic target for serous ovarian cancer

“…Surgical adjuvant chemotherapy is the most common therapeutic method for advanced SOC; however, it has little effect on improving patient survival rate ( 3 ). For this type of malignant tumor with high metastasis rates and fast progression, targeted therapy would be a suitable treatment method ( 8 ). Liposome targeted therapy is an effective strategy for tumors prone to metastasis ( 23 , 24 ).…”

“…At present, surgery supplemented by chemotherapy remains the main treatment option for advanced stages of SOC, and treatment outcomes are unsatisfactory ( 7 ). In recent years, targeted therapy has shown advantages for SOC treatment ( 8 , 9 ). However, in order to treat SOC effectively, more effective therapeutic targets need to be developed ( 10 ).…”

Chemotherapy induced immunogenic cell death alters response to exogenous activation of STING pathway and PD-L1 immune checkpoint blockade in a syngeneic murine model of ovarian cancer

“…The ID8- Trp53 −/− mouse ovarian surface epithelial cells were kindly provided by Dr. Ian McNeish (Imperial College, London, UK) 21 . Mutations in TP53 gene are present in >95% HGSC tumours 2 and thus the recently modified ID8 cell line more closely recapitulates the human HGSC tumour progression. ID8- Trp53 −/− cells were maintained in Dulbecco’s Modified Eagle’s Medium (Sigma Aldrich, Canada) supplemented with 4% fetal bovine serum, 100 µg/mL of penicillin/streptomycin and a solution containing 5 µg/mL of insulin, 2.5 µg/mL of transferrin and 2.5 ng/mL of sodium selenite.…”

“…High grade serous carcinoma of the ovary (HGSC) is a deadly disease with a five-year survival rate of just 45.6% that has seen little improvement over the past few decades 1, 2 . The poor survival rate of HGSC patients can be attributed to a variety of factors including diagnosis at later stages and high rates of resistance and recurrence 3 .…”

The Interaction Between Microorganisms, Metabolites, and Immune System in the Female Genital Tract Microenvironment

“…Whether the metabolic characteristics of the above bacteria are related to the occurrence and development of ovarian tumors and the carcinogenicity of tumors, leading to a unique tumor microenvironment, needs further research. Metabolites are closely related to tumor immunity and tumor development (Turkoglu et al, 2016;Clifford et al, 2018;Szewczyk et al, 2019). Whether the metabolites of the genital tract flora of OC patients participate in tumor immunity and host antitumor immunity, which affects the occurrence, development and metastasis of OC, still needs further research.…”