Biomarkers of drug resistance in ovarian cancer – an update

ABSTRACT

Introduction: Ovarian cancer, consisting predominantly of ovarian carcinoma, is the most lethal gynecologic malignancy. Diagnosis at the advanced stage, particularly in high-grade serous carcinoma which is the most common and clinically aggressive histotype, is a major factor negatively affecting survival, while tumor heterogeneity and chemoresistance often preclude complete elimination of tumor cells even following radical surgery and combination chemotherapy. Recently, inhibition of angiogenesis and inhibition of poly (ADP-ribose) polymerase (PARP) have shown benefit in the treatment of this cancer.

Areas covered: Extensive research has identified molecules associated with resistance to chemotherapy and implicated several biomarkers affecting response to antiangiogenic therapy and PARP inhibition. This review discusses recent data in this field. The presented data, gathered in a PubMed search focusing on the years 2016–2018, focus on regulators of the cell cycle and mitosis, cancer stem cell-related molecules, the immune response, receptor tyrosine kinases and related signaling pathways, BRCA and other DNA repair molecules, microRNAs, and other cancer-associated molecules.

Expert opinion: Future research is likely to focus on histotype-specific analyses of clinical specimens and patient-generated cultures applying cutting-edge molecular technology, in the aim of identifying major regulators of chemotherapy response.

KEYWORDS:

• Ovarian cancer
• heterogeneity
• histology
• progression
• chemotherapy resistance
• angiogenesis
• PARP

Article highlights

• The five main OC histotypes are distinct diagnostic entities with unique genotype and phenotype.

• HGSC is highly heterogeneous at both the inter- and intrapatient level.

• BRCA mutation, HR status and the immune response have a central role in deciding chemoresponse and outcome of patients with HGSC.

• High-throughput technology, including next generation technology (NGS)-based platforms, provides a powerful tool for characterizing resistance-associated signatures.

• Patient-derived xenografts are likely to play an important role in predicting response to chemotherapy and targeted therapy in the future.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.