High-throughput approaches for precision medicine in high-grade serous ovarian cancer
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REVIEW
High‑throughput approaches for precision medicine in high‑grade serous ovarian cancer Meinusha Govindarajan1, Christoph Wohlmuth2,3, Matthew Waas4, Marcus Q. Bernardini2,5* and Thomas Kislinger1,4*
Abstract High-grade serous carcinoma (HGSC) is the most prevalent and aggressive subtype of ovarian cancer. The large degree of clinical heterogeneity within HGSC has justified deviations from the traditional one-size-fits-all clinical management approach. However, the majority of HGSC patients still relapse with chemo-resistant cancer and eventually succumb to their disease, evidence that further work is needed to improve patient outcomes. Advancements in high-throughput technologies have enabled novel insights into biological complexity, offering a large potential for informing precision medicine efforts. Here, we review the current landscape of clinical management for HGSC and highlight applications of high-throughput biological approaches for molecular subtyping and the discovery of putative blood-based biomarkers and novel therapeutic targets. Additionally, we present recent improvements in model systems and discuss how their intersection with high-throughput platforms and technological advancements is positioned to accelerate the realization of precision medicine in HGSC. Keywords: High-grade serous carcinoma, High-throughput technology, Liquid biopsies, Therapeutic targets, Molecular subtypes Background The American Cancer Society estimates that in 2020, 21,750 women will be newly diagnosed with ovarian cancer in the USA and ~ 13,940 will die from the disease [1]. Epithelial ovarian cancer (EOC) represents the fifth most common cause of cancer death overall and is the leading cause of death from gynecologic malignancies in the USA, Canada and Europe [1–3]. EOC is a heterogeneous disease with different types of histologies, molecular and microenvironmental features [4]. Histologically, EOC is traditionally classified into five major subtypes: high-grade serous (HGSC), low-grade serous (LGSC), clear cell, endometrioid and mucinous *Correspondence: [email protected]; [email protected] 1 Department of Medical Biophysics, University of Toronto, Toronto, Canada 2 Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada Full list of author information is available at the end of the article
ovarian cancer [4]. A more recent classification model categorizes EOC into type I and II tumors, where LGSC, endometrioid, mucinous and clear cell carcinomas are classified as type I [5–7]. These neoplasms typically present as large, unilateral, cystic tumors and clinically tend to behave in an indolent fashion [7]. Genetically, type I cancers are characterized by minor chromosomal instability and may harbor BRAF, KRAS and PTEN mutations. Type II cancers, on the other hand, comprise of HGSC, which account for the vast majority of all EOCs, carcinosarcomas and undifferentiated carcinomas. HGSCs have a high degree of genetic instability and
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