High-grade serous ovarian cancer: the clone wars

Abstract

Background: The last 5 years' studies using next-generation sequencing provided evidences that many types of solid tumors present spatial and temporal genetic heterogeneity and are composed of multiple populations of genetically distinct subclones that evolve over time following a pattern of branched evolution. The evolutionary nature of cancer has been proposed as the major contributor to drug resistance and treatment failure. In this review, we present the current state of knowledge about the clonal evolution of high-grade serous ovarian cancer and discuss the challenge that clonal evolution poses for efforts to achieve an optimal cancer control.

Methods: A systemic search of peer-reviewed articles published between August 2007 and October 2016 was performed using PUBMED and Google Scholar database.

Results and conclusions: Recent studies using next-generation sequencing have allowed us to look inside the evolutionary nature of high-grade serous ovarian cancer, which in the light of current evidence can explain the relapsing course of the disease frequently observed in the clinical practice. Since only minimal improvement in the survival of patients treated with standard therapy has been observed in the last decade, novel molecular targeted therapies are of great interest in high-grade serous ovarian cancer. However, both spatial and temporal intratumoral genetic heterogeneity is a major challenge for personalized medicine, and greater knowledge of the molecular rules that drive tumor evolution through space and time is required to achieve a long-term clinical benefit from personalized therapy.

Keywords: Clonal evolution; Drug resistance; Genetic heterogeneity; Genomic instability; Ovarian cancer.