Immune system and DNA repair defects in ovarian cancer: Implications for locoregional approaches

Alberto Farolfi, Giorgia Gurioli, Paola Fugazzola, Salvatore Luca Burgio, Claudia Casanova, Giorgia Ravaglia, Amelia Altavilla, Matteo Costantini, Andrea Amadori, Massimo Framarini, Luca Ansaloni, Ugo De Giorgi

Research output: Contribution to journalReview article

Abstract

In the last few years, substantial progress has been made in the treatment of ovarian cancer, with increased knowledge about the biology of the disease. Ovarian cancer is a neoplasm strongly linked to defects in DNA repair mechanisms, where deficiency in the homologous recombination (HR) system results in a better response of ovarian cancers to therapy, whether platinum-based chemotherapy, anthracyclines, or poly (ADP-ribose) polymerase (PARP) inhibitors. More recently, it has been demonstrated that different ovarian cancer histotypes may have different immunogenicity. Interestingly, defects in HR systems are associated more frequently with higher tumor infiltrating lymphocytes, providing a rationale for developing combination therapy with immune-modulating agents and PARP inhibitors. Again, locoregional therapies combining heat shock and chemotherapy delivery have been shown to induce an anticancer immune response in vitro. Thus, the potential for locoregional therapeutic approaches that may impact the immune system, perhaps in combination with immune-modulating agents or PARP inhibitors, needs to be further explored. With this premise, we reviewed the main biological and clinical data demonstrating a strict interplay between the immune system, DNA repair mechanisms, and intraperitoneal therapies in ovarian cancer, with a focus on potential future therapeutic implications.

Original languageEnglish
Article number2569
JournalInternational Journal of Molecular Sciences
Volume20
Issue number10
DOIs
Publication statusPublished - May 2 2019

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Keywords

  • DNA repair defects
  • Immune system
  • Immunotherapy
  • Inflammation
  • Ovarian cancer
  • PARP-inhibitors

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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