The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors

Lorena Incorvaia; Tancredi Didier Bazan Russo; Valerio Gristina; Alessandro Perez; Chiara Brando; Clarissa Mujacic; Emilia Di Giovanni; Marco Bono; Silvia Contino; Carla Ferrante Bannera; Maria Concetta Vitale; Andrea Gottardo; Marta Peri; Antonio Galvano; Daniele Fanale; Giuseppe Badalamenti; Antonio Russo; Viviana Bazan

doi:10.1038/s41698-024-00672-0

npj Precision Oncology (Sep 2024)

The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors

Lorena Incorvaia,
Tancredi Didier Bazan Russo,
Valerio Gristina,
Alessandro Perez,
Chiara Brando,
Clarissa Mujacic,
Emilia Di Giovanni,
Marco Bono,
Silvia Contino,
Carla Ferrante Bannera,
Maria Concetta Vitale,
Andrea Gottardo,
Marta Peri,
Antonio Galvano,
Daniele Fanale,
Giuseppe Badalamenti,
Antonio Russo,
Viviana Bazan

Affiliations

Lorena Incorvaia: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Tancredi Didier Bazan Russo: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Valerio Gristina: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Alessandro Perez: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Chiara Brando: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Clarissa Mujacic: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Emilia Di Giovanni: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Marco Bono: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Silvia Contino: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Carla Ferrante Bannera: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Maria Concetta Vitale: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Andrea Gottardo: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Marta Peri: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Antonio Galvano: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Daniele Fanale: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Giuseppe Badalamenti: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Antonio Russo: Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of Palermo
Viviana Bazan: Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), Section of Medical Oncology, University of Palermo

DOI: https://doi.org/10.1038/s41698-024-00672-0
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 12

Abstract

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Abstract Homologous recombination (HR) and mismatch repair (MMR) defects are driver mutational imprints and actionable biomarkers in DNA repair-defective tumors. Although usually thought as mutually exclusive pathways, recent preclinical and clinical research provide preliminary evidence of a functional crosslink and crosstalk between HRR and MMR. Shared core proteins are identified as key players in both pathways, broadening the concept of DNA repair mechanism exclusivity in specific tumor types. These observations may result in unexplored forms of synthetic lethality or hypermutable tumor phenotypes, potentially impacting the cancer risk management, and considerably expanding in the future the therapeutic window for DNA repair-defective tumors.

Published in npj Precision Oncology

ISSN: 2397-768X (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.nature.com/npjprecisiononcology/

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