Ovarian Cancer-Insights into Platinum Resistance and Overcoming It

• Published in: Medicina (Kaunas, Lithuania) Vol. 59; no. 3; p. 544
• Main Authors: Havasi, Andrei, Cainap, Simona Sorana, Havasi, Ana Teodora, Cainap, Calin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer therapies; Carcinoma, Ovarian Epithelial - drug therapy; Causes of; Chemotherapy; Chemotherapy, Combination; Complications and side effects; Copper; Dosage and administration; Drug resistance; Drug Resistance, Neoplasm; Drug therapy; Family medical history; Female; Genetic aspects; Health aspects; Humans; Lung cancer; Medical prognosis; Methods; Mutation; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; overcoming platinum resistance; Patients; Platinum - pharmacology; Platinum - therapeutic use; Platinum compounds; platinum resistance; platinum resistance mechanisms; Prevention; Review; Surgery; Tumor Microenvironment; Tumors; Romania; ovarian cancer; overcoming platinum resistance; platinum resistance mechanisms; platinum resistance
• ISSN: 1648-9144; 1010-660X; 1648-9144
• DOI: 10.3390/medicina59030544

Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells' resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients' poor prognosis, discussing current strategies, novel combinations, and therapeutic agents.