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

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.

Enhancing the anti-tumor response by combining DNA damage repair inhibitors in the treatment of solid tumors.

The anti-cancer efficacy of anti-malignancy therapies is related to DNA damage. However, DNA damage-response mechanisms can repair DNA damage, failing anti-tumor therapy. The resistance to chemotherapy, radiotherapy, and immunotherapy remains a clinical challenge. Thus, new strategies to overcome these therapeutic resistance mechanisms are needed. DNA damage repair inhibitors (DDRis) continue to be investigated, with polyadenosine diphosphate ribose polymerase inhibitors being the most studied inhibitors. Evidence of their clinical benefits and therapeutic potential in preclinical studies is growing. In addition to their potential as a monotherapy, DDRis may play an important synergistic role with other anti-cancer therapies or in reversing acquired treatment resistance. Here we review the impact of DDRis on solid tumors and the potential value of combinations of different treatment modalities with DDRis for solid tumors.