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Published on: July 25, 2020
Successes and limitations of targeted cancer therapy in ovarian cancer
Giovanna Damia1, Cristiana Sessa
1Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy.
Abstract:
In ovarian cancer, the clinical development of anticancer agents targeting DNA repair has been associated with significant results because of the elucidation of the different types of damages and repair systems, including PARP. The discovery of the BRCA mutation and its role in ovarian cancer and the clinical application of the concept of synthetic lethality have been the rationale for the successful testing of PARP inhibitors in BRCA mutated ovarian cancer patients. The recent knowledge of the molecular features of low grade ovarian cancer and the application of the concept of synthetic lethality also in this well-defined pathological entity have prompted the clinical evaluation of a combination of PI3K/MEK inhibitors, the first results of which have been already reported.
Insights
PARP inhibitors show success in BRCA-mutated ovarian cancer by targeting DNA repair. New research explores PI3K/MEK inhibitors for low-grade ovarian cancer, applying synthetic lethality principles.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA repair mechanisms are crucial targets in ovarian cancer therapy.
- Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promise, particularly in BRCA-mutated cases, leveraging synthetic lethality.
- Recent insights into low-grade ovarian cancer molecular features enable new therapeutic strategies.
Purpose of the Study:
- To review the clinical development of DNA repair-targeting agents in ovarian cancer.
- To highlight the role of synthetic lethality in the success of PARP inhibitors.
- To discuss the emerging evaluation of PI3K/MEK inhibitor combinations in low-grade ovarian cancer.
Main Methods:
- Literature review of DNA repair inhibitors in ovarian cancer.
- Analysis of clinical trial outcomes for PARP inhibitors in BRCA-mutated patients.
- Examination of preclinical and clinical data for PI3K/MEK inhibitors in low-grade ovarian cancer.
Main Results:
- PARP inhibitors are effective in BRCA-mutated ovarian cancer patients.
- The concept of synthetic lethality underpins the efficacy of these targeted therapies.
- Early results from PI3K/MEK inhibitor combinations in low-grade ovarian cancer are emerging.
Conclusions:
- Targeting DNA repair, particularly with PARP inhibitors, is a validated strategy in ovarian cancer.
- Synthetic lethality provides a rational basis for developing novel ovarian cancer treatments.
- Combination therapies like PI3K/MEK inhibitors represent a promising new avenue for low-grade ovarian cancer.
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