Error-prone DNA repair pathways as determinants of immunotherapy activity: an emerging scenario for cancer treatment.

Abstract

Defects in DNA repair machinery play a critical role in the pathogenesis and progression of human cancer. When they occur, the tumor cells activate error-prone mechanisms which lead to genomic instability and high mutation rate. These defects represent, therefore, a cancer Achilles'heel which could be therapeutically exploited by the use of DNA damage response inhibitors. Moreover, experimental and clinical evidence indicates that DNA repair deregulation has a pivotal role also in promoting immune recognition and immune destruction of cancer cells. Indeed, immune checkpoint inhibitors have received regulatory approval in tumors characterized by high genomic instability, such as melanomas and lung cancer. Here, we discuss how deregulation of DNA repair, through activation of error-prone mechanisms, increases immune activation against cancer. Finally, we address the potential strategies to use DNA repair components as biomarkers and/or therapeutic targets to empower immune-oncology treatment of human cancer.

• Authors: Daniele Caracciolo, Caterina Riillo, Mariamena Arbitrio, Maria Teresa Di Martino, Pierosandro Tagliaferri, Pierfrancesco Tassone
• Journal: International journal of cancer (Int J Cancer) Vol. 147 Issue 10 Pg. 2658-2668 (11 15 2020) ISSN: 1097-0215 [Electronic] United States
• PMID: 32383203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2020 UICC.

Chemical References

• Biomarkers, Tumor
• Immune Checkpoint Inhibitors
• DNA Repair Enzymes

Topics

• Biomarkers, Tumor (genetics)
• DNA Repair
• DNA Repair Enzymes
• Genomic Instability
• Humans
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Neoplasms (drug therapy, genetics)