Combining epigenetic drugs with other therapies for solid tumours — past lessons and future promise

Daphné Morel, Daniel Jeffery, Sandrine Aspeslagh, Geneviève Almouzni, Sophie Postel-Vinay

    Research output: Contribution to journalReview articlepeer-review

    304 Citations (Scopus)

    Abstract

    Epigenetic dysregulation has long been recognized as a key factor contributing to tumorigenesis and tumour maintenance that can influence all of the recognized hallmarks of cancer. Despite regulatory approvals for the treatment of certain haematological malignancies, the efficacy of the first generation of epigenetic drugs (epi-drugs) in patients with solid tumours has been disappointing; however, successes have now been achieved in selected solid tumour subtypes, thanks to the development of novel compounds and a better understanding of cancer biology that have enabled precision medicine approaches. Several lines of evidence support that, beyond their potential as monotherapies, epigenetic drugs could have important roles in synergy with other anticancer therapies or in reversing acquired therapy resistance. Herein, we review the mechanisms by which epi-drugs can modulate the sensitivity of cancer cells to other forms of anticancer therapy, including chemotherapy, radiation therapy, hormone therapy, molecularly targeted therapy and immunotherapy. We provide a critical appraisal of the preclinical rationale, completed clinical studies and ongoing clinical trials relating to combination therapies incorporating epi-drugs. Finally, we propose and discuss rational clinical trial designs and drug development strategies, considering key factors including patient selection, tumour biomarker evaluation, drug scheduling and response assessment and study end points, with the aim of optimizing the development of such combinations.

    Original languageEnglish
    Pages (from-to)91-107
    Number of pages17
    JournalNature Reviews Clinical Oncology
    Volume17
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2020

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