Sensitivity and resistance to treatment in the primary management of epithelial ovarian cancer

Abstract

Ovarian carcinoma is the most lethal gynaecologic malignancy. Despite wide initial sensibility to chemotherapy especially to platinum-based regimens, the vast majority of patients with advanced stages of the disease develop recurrences and subsequent resistance to treatments. Ovarian cancer is actually considered as a heterogeneous disease at the clinical, histological and molecular level. In this review, the mechanisms of intrinsic sensitivity or resistance to treatment, especially to platinum-based chemotherapy are considered with particular reference to the significance of tumour heterogeneity. The molecular features involved in acquired resistance are reviewed and the current hypotheses are discussed. In particular, potential disruptions of the DNA reparation pathways are highlighted.

Keywords: ARID1A; ASCO; AT-rich interactive domain 1A gene; ATM; ATR; American Society of Clinical Oncology; B-RAF; BER; BRCA1/2; CCNE1; CTR1; DNA repair pathways; EGFR; ERCC1; FANCD2; FIGO; Fanconi anaemia, complementation group D2; GIST; GST; HER2; HR; Heterogeneity; International Federation of Gynecology and Obstetrics; K-RAS; MAPK; MRP2; Molecular subtypes; NER; OS; Ovarian cancer; PARP; PTEN; RFS; Resistance; STIC; VEGF; ataxia telangiectasia and Rad3 related; ataxia telangiectasia mutated; base excision repair; breast cancer gene 1 or 2; copper transporter 1; cyclin E1; epidermal growth factor receptor; excision repair cross-complementation group 1; gastro-intestinal stromal tumour; gluthatione S-transferase; homologous recombination; human epidermal growth factor receptor-2; mitogen-activated protein kinases; multidrug resistance protein 2; nucleotide excision repair; overall survival; phosphatase and tensin homolog; poly ADP ribose polymerase; relapse-free survival; serous tubal intraepithelial carcinoma; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; v-raf murine sarcoma viral oncogene homolog B1; vascular endothelial growth factor.