Deciphering the Molecular Mechanisms behind Drug Resistance in Ovarian Cancer to Unlock Efficient Treatment Options

Author:

Nunes Mariana12ORCID,Bartosch Carla345,Abreu Miguel Henriques36,Richardson Alan7ORCID,Almeida Raquel189,Ricardo Sara1910ORCID

Affiliation:

1. Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal

2. Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal

3. Porto Comprehensive Cancer Center Raquel Seruca (PCCC), Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072 Porto, Portugal

4. Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072 Porto, Portugal

5. Cancer Biology & Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (CI-IPO-Porto), Health Research Network (RISE@CI-IPO-Porto), Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072 Porto, Portugal

6. Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072 Porto, Portugal

7. The School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Thornburrow Drive, Stoke-on-Trent ST4 7QB, Staffordshire, UK

8. Biology Department, Faculty of Sciences, University of Porto (FCUP), 4169-007 Porto, Portugal

9. Associate Laboratory i4HB, Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal

10. UCIBIO—Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal

Abstract

Ovarian cancer is a highly lethal form of gynecological cancer. This disease often goes undetected until advanced stages, resulting in high morbidity and mortality rates. Unfortunately, many patients experience relapse and succumb to the disease due to the emergence of drug resistance that significantly limits the effectiveness of currently available oncological treatments. Here, we discuss the molecular mechanisms responsible for resistance to carboplatin, paclitaxel, polyadenosine diphosphate ribose polymerase inhibitors, and bevacizumab in ovarian cancer. We present a detailed analysis of the most extensively investigated resistance mechanisms, including drug inactivation, drug target alterations, enhanced drug efflux pumps, increased DNA damage repair capacity, and reduced drug absorption/accumulation. The in-depth understanding of the molecular mechanisms associated with drug resistance is crucial to unveil new biomarkers capable of predicting and monitoring the kinetics during disease progression and discovering new therapeutic targets.

Publisher

MDPI AG

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