Sensitivity and resistance to treatment in the primary management of epithelial ovarian cancer.
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.
Department of Surgical Oncology, Montpellier Cancer Institute (ICM), 34298 Montpellier, France. Electronic address: Pierre-Emmanuel.Colombo@icm.unicancer.fr.
Pierre-Emmanuel
PE
Colombo
Departement of Medical Oncology, Montpellier Cancer Institute (ICM), 34298 Montpellier, France.
Michel
M
Fabbro
Identity and Tumoral Plasticity, (INSERM U896), Research Cancer Institute IRCM Montpellier Cancer Institute, 34298 Montpellier, France.
Charles
C
Theillet
Department of pathology, Montpellier Cancer Institute (ICM), 34298 Montpellier, France.
Frédéric
F
Bibeau
Department of Surgical Oncology, Montpellier Cancer Institute (ICM), 34298 Montpellier, France.
Philippe
P
Rouanet
Departement of Medical Oncology, Centre Léon Bérard, 69008 Lyon, France.
Isabelle
I
Ray-Coquard
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D004260:DNA Repair / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds
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