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A Visit with Kristian Helin

In September 2018, Kristian Helin, PhD, moved to the US from the University of Copenhagen to become Chair of the MSK Cell Biology Program and Director of the Center for Epigenetics Research, both part of the Sloan Kettering Institute (SKI). In his dual role, this cell biologist is leading studies to understand epigenetic drivers of cancer and how they may be reversed.

What is epigenetics?

Genes are determined by DNA, the molecules inside cells that pass information from one generation to the next.

Epigenetics regulates the activity, or expression, of genes, ensuring that cells function properly. When epigenetic regulators malfunction, cancer can develop.

What have we learned about this system?

In the past decade, scientists have learned that abnormalities in the epigenetic system cause many types of cancer. And we’ve learned that unlike mutations in DNA, which are permanent, epigenetic changes are reversible and highly responsive to medications.

This knowledge has led to new drugs that target these changes and return gene functions to their original state. The fi rst one was developed by Dr. Paul Marks—now President Emeritus at MSK—and approved by the FDA in 2006 to treat a type of lymphoma.

Eleven years later, MSK introduced a new class of epigenetic drugs designed to reverse mutations that affect cell metabolism. The first drug, enasidenib, approved in 2017, and a subsequent one, ivosidenib, have proven effective in some patients with treatment-resistant acute myeloid leukemia (AML).

Are there many epigenetic drugs available?

Not yet. But the pipeline is expanding.

My lab colleagues and I have been pioneers in epigenetics, from explaining how the system works to identifying targetable proteins—the fi rst step in drug development. Over the last 15 years, we’ve developed potential new therapies that have now entered the clinical trials phase. The patients enrolled have lymphomas or other cancers with identifi able epigenetic targets. We’ve also found a potential new treatment for an epigenetic mutation that causes an aggressive pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG).

What’s exciting is that the pace of discovery in epigenetics has quickened.

Can epigenetic drugs be combined with other forms of cancer therapy?

Yes, I believe so. For instance, immunotherapy harnesses a patient’s own immune system to recognize and kill cancer cells. We don’t completely understand why one patient can achieve complete remission with an immunotherapy, while someone else with the exact same cancer type does not respond well to it.

Epigenetic drugs could make immunotherapy more effective by normalizing the state of previously altered genes.

Is philanthropic funding important to your work?

Absolutely. We can develop a novel approach to understanding cancer—but to jump-start it we need help from donors who are as passionate about our work as we are.

MSK is an amazing place, with a wonderful and generous philanthropic community. I was drawn here because the opportunities to make a difference in people’s lives are so profound.