Despite our increasing knowledge of the basis of cancer, progress in treatment of the common cancers is still suboptimal. Most new therapy approaches focus on genetic abnormalities. Deep sequencing of cancer genomes has allowed targeting of specific driver mutations, which can provide robust initial responses but often has short durability with evolution of resistance.
“Epigenetics” refers to heritable changes in gene expression patterns that do not rely on primary DNA sequence changes. If DNA is like the hard drive that contains the information to guide every cellular function, then epigenetic modulation acts as software that regulates the packaging of DNA to guide potential for gene expression patterns. Epigenetic control guides cell type fates during embryogenesis and adult cell renewal.
A key example of epigenetic alteration in cancer is abnormal silencing of nonmutated tumor suppressor genes, which serves as an alternative to mutations for effecting loss of gene function. A recent exciting indication of the importance of epigenetic changes is the finding, in virtually every cancer type, of mutations in genes that encode many proteins that regulate the epigenome . Deciphering the ramifications of these genetic changes is a major imperative for cancer research.
Only in the past decade have we begun to fully recognize the extent to which cancer cells use epigenetics to abnormally reprogram cells. This new understanding includes the appreciation of the large numbers of mutations in cancer affecting genes that regulate epigenetic control. These coalitions of epigenetic and genetic abnormalities are guiding our thinking about epigenetic therapy strategies for cancer. The advancement of genome sequencing in the clinical arena would enable further advances toward personalized medical care. Already there are signs that this form of treatment, using older agents and the novel small molecules that are being developed, could lead to a true change in cancer management. The potential to reverse cancer-associated epigenetic abnormalities to reprogram neoplastic cells is a growing reality, and the next few years may see increasing excitement if signs of clinical efficacy continue to emerge.
There are only few centers in the US that provide relatively safe and effective therapies based on this approach.