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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Epigenetic modulators as therapeutic targets in prostate cancer
TL;DR: The role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management are highlighted, highlighting the most important epigenetic alterations in prostate cancer.
Journal ArticleDOI
Epigenetic therapy for solid tumors: from bench science to clinical trials
Yen-Yi Juo,Xue Jun Gong,Xue Jun Gong,Ankita Mishra,Xiao Cui,Stephen B. Baylin,Nilofer S. Azad,Nita Ahuja +7 more
TL;DR: It is important to reconsider the optimal patient selection, drug regimen, study design, and outcome measures when pursuing future trials when pursuing epigenetic agents in order to discover the full potential of this new therapeutic modality.
Journal ArticleDOI
Kaempferol Modulates DNA Methylation and Downregulates DNMT3B in Bladder Cancer.
TL;DR: Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer and is reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs), but whether Kae can inhibitDNA methylation remains unclear.
Journal ArticleDOI
New Strategies in Lung Cancer: Epigenetic Therapy for Non-Small-Cell Lung Cancer
TL;DR: The current status of attempts to target the epigenome, heritable modifications of DNA, histones, and chromatin that may act to modulate gene expression independently of DNA coding alterations, in NSCLC are reviewed and the potential for combinatorial and sequential treatment strategies are reviewed.
Journal ArticleDOI
Compendium of aberrant DNA methylation and histone modifications in cancer.
Naoko Hattori,Toshikazu Ushijima +1 more
TL;DR: The major concepts of cancer epigenetics are summarized, placing emphasis on history, to establish that aberrant epigenetic alterations are involved in cancer development and progression, along with mutations and chromosomal losses.
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TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
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