The future of epigenetic therapy in solid tumours--lessons from the past.
TLDR
It is hypothesized that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose, and could give these agents a prominent place in cancer management.Abstract:
The promise of targeting epigenetic abnormalities for cancer therapy has not been realized for solid tumours, although increasing evidence is demonstrating its worth in haematological malignancies. In fact, true clinical efficacy in haematopoietic-related neoplasms has only become evident at low doses of epigenetic-targeting drugs (namely, inhibitors of histone deacetylase and DNA methyltransferases). Describing data from preclinical studies and early clinical trial results, we hypothesize that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose. We suggest that such optimization of drug dosing and scheduling of currently available agents could give these agents a prominent place in cancer management--when used alone or in combination with other therapies. If so, optimal use of these known agents might also pave the way for the introduction of other agents that target the epigenome.read more
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Journal ArticleDOI
Molecular Determinants of Gastrointestinal Cancers
Francesca Battaglin,Giovanni Randon,Alessandra Raimondi,Filippo Pagani,Hiroyuki Arai,Filippo Pietrantonio,Heinz-Josef Lenz +6 more
Book ChapterDOI
Epigenetic therapy and DNA damage response
TL;DR: In this article , the authors discuss current and future applications of the mechanistic interplays between chromatin regulation and DNA repair for improving the efficacy and safety of cancer treatments and discuss the potential of epigenetic regulators of DNA architecture to alter cells susceptibility to DNA-damaging agents used in cancer therapies.
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