The 13th symposium

Speech

Special　Lecture1

“Cancer genomic medicine for chromatin regulator-deficient cancers”
Hideaki Ogiwara, Chief, Division of Cancer Therapeutics, National Cancer Center Research Institute

Cancer genomic medicine is individualized cancer medicine based on the genetic abnormalities in cancers. At present, genetic abnormalities covered by cancer genomic medicine are mainly activating mutations in cancer genes, and treatment of defective genetic abnormalities, such as those in tumor suppressor genes, remains largely unestablished. Recent cancer genome analyses have revealed defects in various chromatin regulatory genes in a variety of cancers. Defects in the chromatin regulators result in dependence on factors functionally complementary to them, and this is a weakness of cancer that can be exploited. In addition, defects in chromatin regulators cause vulnerabilities in functional pathways, which may also be a weakness that can be targeted. Promising treatments could be expected to be established for chromatin regulator-deficient cancers by detecting and targeting these weaknesses. In this presentation, I would like to introduce the exploration of therapeutic targets based on defects in chromatin regulatory genes, demonstrate scientific evidence accumulated based on analyses of the underlying mechanisms, and discuss the feasibility of clinical application through drug development.

Special　Lecture2

“Vitamin C and Epigenetics”
Akihito Ishigami, Molecular Regulation of Aging, Research Team for Functional Biogerontology,
Tokyo Metropolitan Institute of Gerontology Director, Team Leader

Epigenetics is defined as “study of changes in the gene expressions or cell phenotypes derived through cell division, without alterations in the deoxyribonucleic acid (DNA) sequence.” Unlike permanent gene mutations, epigenetics exhibits plasticity and could change under the influence of external factors, such as the environment and lifestyle. DNA methylation and histone modifications are well known representative mechanisms in epigenetics.
Vitamin C (L-ascorbic acid) has many physiological effects, such as antioxidant and collagen polymerization activities. Recently, vitamin C has been revealed to be involved in epigenetics as a cofactor for DNA demethylase (Ten-eleven translocation [Tet]). Namely, vitamin C can alter gene expressions in human embryonic stem (ES) cells, liver, and epidermal cells. In addition, vitamin C can prevent hematopoietic stem cells from proliferating in an unregulated manner. Furthermore, vitamin C has also been found to be involved, as a cofactor for histone demethylases, in cell reprogramming and inflammatory cytokine expression. It is expected that new physiological functions of vitamin C will continue to be discovered in the future from the perspective of epigenetics.
In this presentation, I would like to review how the involvement of vitamin C in epigenetics was discovered and its history and introduce our latest research results.