Clinical and molecular features of platinum resistance in ovarian cancer
Isabel Miras, Purificación Estévez-García, Sandra Muñoz-Galván
Abstract
Ovarian cancer is the most lethal of all the gynecological tumors despite remarkable advances in our understanding of its molecular biology. The cornerstone treatment remains cytoreductive surgery followed by platinum-based chemotherapy. Recently, the addition of targeted therapies, such as PARP inhibitors, as first-line maintenance has led to outstanding improvements, mainly in BRCA mutated and homologous recombination deficient tumors. However, a significant proportion of patients will experience recurrence, primarily due to platinum resistance, which ultimately result in fatality. Among these patients, primary platinum-resistant have a particularly dismal prognosis due to their low response to current available therapies, historical exclusion from clinical trials, and the absence of validated biomarkers. In this review, we discuss the concept of platinum resistance in ovarian cancer, the clinical and molecular characteristics of this resistance, and the current and new treatment options for these patients. • Primary platinum-resistant ovarian cancer (PPROC) patients show bad prognosis and lack available therapies or biomarkers. • PPROC shows specific molecular features and resistance to cisplatin through several mechanisms. • A better understanding of PPROC biology will allow to discover new targets of potential diagnostic or therapeutic interest.