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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Non-Invasive Early Molecular Detection of Gastric Cancers.
TL;DR: A comprehensive review demonstrates how liquid biopsy may be beneficial in identifying and optimizing new diagnostic approaches for gastric cancer, and summarizes recently reported biomarkers based on DNA methylation, microRNA, long noncoding RNA, circular RNA, or extracellular vesicles (exosomes) for the detection of GC.
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Inhibition of the H3K9 methyltransferase G9A attenuates oncogenicity and activates the hypoxia signaling pathway.
Jolene Caifeng Ho,Lissa Nurrul Abdullah,Qing You Pang,Sudhakar Jha,Edward Kai-Hua Chow,Henry Yang,Hiroyuki Kato,Lorenz Poellinger,Lorenz Poellinger,Jun Ueda,Kian Leong Lee +10 more
TL;DR: G9A is a key mediator of oncogenic processes in breast cancer cells and G9A inhibition by BIX-01294 can successfully attenuate oncogenicity even in hypoxia.
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Molecular pathogenesis and therapeutic implications in pediatric high-grade gliomas
TL;DR: This review summarizes the current state of knowledge about the molecular characterization of pediatric HGG in correlation to the revised World Health Organization (WHO) classification, as well as provides an overview of some targeted treatment approaches in the modern clinical management of high‐grade gliomas.
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Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015)
TL;DR: Clinical development of small- and macromolecular anti-CSC therapeutics is underway and few of these agents act on validated targets such as kinases, e.g., kinase inhibitors, polypeptides, etc.
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Characterization of RON protein isoforms in pancreatic cancer: implications for biology and therapeutics
Jeffery Chakedis,Randall French,Michele L. Babicky,Dawn Jaquish,Evangeline Mose,Peter Cheng,Patrick Holman,Haleigh Howard,Jaclyn Miyamoto,Paula Porras,Zakk Walterscheid,Carsten Schultz-Fademrecht,Christina Esdar,Oliver Schadt,Jan Eickhoff,Andrew M. Lowy +15 more
TL;DR: It is found that transcription of RON isoforms is regulated by promoter hypermethylation as the DNA demethylating agent 5-aza-2′-deoxycytidine decreased all RON transcripts in a subset of pancreatic cancer cell lines.
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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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