The DNA damage response pathway as a land of therapeutic opportunities for colorectal cancer

Annals of Oncology : Official Journal of the European Society for Medical Oncology
G MauriA Sartore-Bianchi

Abstract

Colorectal cancer (CRC) represents a major cause of cancer deaths worldwide. Although significant progress has been made by molecular and immune therapeutic approaches, prognosis of advanced stage disease is still dismal. Alterations in the DNA damage response (DDR) pathways are emerging as novel targets for treatment across different cancer types. However, even though preclinical studies have shown the potential exploitation of DDR alterations in CRC, systematic and comprehensive testing is lagging and clinical development is based on analogies with other solid tumors according to a tissue-agnostic paradigm. Recently, functional evidence from patient-derived xenografts and organoids have suggested that maintenance with PARP inhibitors might represent a therapeutic opportunity in CRC patients previously responsive to platinum-based treatment. In this review, we highlight the most promising preclinical data and systematically summarize published clinical trials in which DDR inhibitors have been used for CRC and provide evidence that disappointing results have been mainly due to a lack of clinical and molecular selection. Future preclinical and translational research will help in better understanding the role of DDR alterations i...Continue Reading

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Citations

Aug 23, 2020·Cancers·Federica MarmorinoChiara Cremolini
Oct 23, 2020·Cancer Treatment Reviews·Gianluca MauriAndrea Sartore-Bianchi
Apr 18, 2021·Nature Reviews. Clinical Oncology·Federica Di NicolantonioAlberto Bardelli
May 28, 2021·ESMO Open·G PatelliA Sartore-Bianchi
Jun 26, 2021·IScience·Simone Di FrancoGiorgio Stassi
Jun 25, 2021·World Journal of Gastrointestinal Oncology·Keun-Yeong Jeong, Minhee Park
Aug 10, 2021·World Journal of Clinical Oncology·Elena MaccaroniRossana Berardi
Sep 2, 2021·Journal of the National Cancer Institute·Roberto MorettoChiara Cremolini
Oct 5, 2021·Acta Oncologica·R L EefsenE Høgdall

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