Molecular and Cellular Mechanisms of Cancers: Ovarian Cancer

Dear Colleagues,

Epithelial ovarian cancer (OC) is the leading cause of death among gynecological cancers. No effective screening strategies for early detection are available and the majority of patients are diagnosed with advanced stage disease. Front-line debulking surgery and platinum-based chemotherapeutic regimens have been the standard of care for almost 40 years worldwide.

Large efforts have been made in the last decade to better understand the cellular and molecular biology of this highly heterogeneous malignancy. Almost 10 years ago, OCs were proposed to be classified into Type I (low grade tumors harboring BRAF, KRAS, and PTEN mutations) and Type II tumors (high-grade tumors characterized by p53, BRCA1/2 mutations). Subsequent genomic studies then subdivided serous high-grade OC into four molecular subgroups, but this classification is still not yet clinically applied. However, the realization that ovarian cancer is composed of several different subtypes with different molecular landscapes, the improved understanding of the genomics of these subtypes, and the development of new active biological agents all promise to improve ovarian cancer outcomes and mortality. The change in perspective from one disease with several epithelial subtypes to several distinct diseases has begun to affect treatment strategies. The shift in trial design toward eligibility restriction rather than testing agents in unselected populations provides potential opportunities to improve therapy in targeted populations, as it has been observed for PARP inhibitors for patients harboring BRCA mutation or homologous recombination deficiency.

Although we are entering into the era of personalized medicine, for the majority of OC patients we are still dealing with the development of an incurable state of platinum-resistant disease that keeps the five-year survival rate below 40%. These data justify the incredible effort to change the standard of care with a considerable number of clinical trials and in particular with the introduction of translational studies in the design of clinical trials to better understand the molecular mechanisms driving OC onset, progression and the development of chemoresistance and to better design tailored therapeutic interventions.

The main focus of this Special Issue will be to provide a platform for clinicians and translational researchers for the most recent breakthroughs in the definition of the molecular pathways/mechanisms related to the natural history of this life-threatening disease.

Potential topics may include:

1. Molecular characterizations associated with ovarian cancer onset, progression, dissemination into the peritoneal cavity, and the development of chemoresistance.
2. Models of development and growth
3. New molecular-based therapeutic strategies
4. Identification of prognostic/predictive biomarkers
5. Characterization of metabolic alterations
6. Immunotherapy

Dr. Delia Mezzanzanica
Dr. Gustavo Baldassarre
Dr. Stefano Indraccolo
Dr. Marina Bagnoli
Guest Editors

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