Cancer Epigenetics

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Highlighting developments in cancer therapies.
Image Caption: 
Conference attendee and postdoctoral fellow, Laura Garcia Prat (pictured) works in the laboratory of Dr. John Dick, Princess Margaret Cancer Center, part of the University Health Network.

Conference: Cancer Epigenetics: New Mechanisms, New Therapies, Keystone Symposia, February 10-14, Breckenridge, Colorado, USA.

Conference Highlight: Chemical modifications on RNA, similar to those in its DNA and histone counterparts, contribute to gene expression control and may play an important role in cancer. Proteins that write, read and erase these modifications are highly mutated in Acute Myeloid Leukemia and contribute to disease initiation and progression.

Conference Summary: Methodologies based on next-generation sequencing have enabled the deciphering of modifications in low-abundance RNA species, including messenger RNA and long non-coding RNAs. The probing of the chemistry and the cellular machineries that write, read and erase these modifications has exposed the role of a new layer of dynamic epigenetic regulation termed epitranscriptomics. The knowledge emerging from epitranscriptome research is now becoming relevant to biological and medical questions as best exemplified by cancer research.

Chromatin organization in the nucleus provides a large repertoire of information in addition to genetically coded information. A major goal for the field of cancer epigenetics is now to understand how histones, the major protein components of chromatin, can mark functional regions of the genome through their variants or post-translational modifications, along with non-coding RNA and other chromatin regulators. Errors in the establishment and propagation of these chromatin components, possibly involving imbalance in their deposition pathways, can lead to dysregulation of genome functions and pathological outcomes, such as cancer.

Currently approved immune-targeting therapies for cancer consist primarily of biologics-based approaches to target cell surface molecules on tumour or immune cells. However, to maximize the benefit of our emerging understanding of immune-oncology, it will be necessary to develop agents that impact the tumour through a variety of mechanisms. Direct targeting of tumour cells to facilitate immune recognition, altering the tumour microenvironment to enable effective immune function and enhancing both innate and adaptive immune responses are potential routes to achieving therapeutic benefit. Thus, it is necessary to consider the cells that comprise the tumour milieu in their entirety and not in isolation. Efforts to understand the next therapeutic benefit of epigenetic agents despite the diverse effects on individual cell populations are needed, particularly as it pertains to complementing or enabling immune-therapies in cancer.