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Audio Interview

Epigenetic pharmaceuticals used in the clinic

Published on April 27, 2020   17 min

A selection of talks on Cancer

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Interviewer: Dr. Thomas Paul, thank you very much for taking the time to do this interview with us today, to discuss the role of epigenetic drugs in the clinic. Let me just start by asking you: are epigenetic drugs often included within chemotherapy cocktails, and if so, what are the added benefits of including such therapeutics? Dr. Paul: The original rationale for using combinations of epigenetic drugs in chemotherapy was dictated by some early preclinical observations that showed that some of these early first-generation epigenetic drugs (such as the histone deacetylase inhibitors or the DNA methyltransferase inhibitors) were showing some promising combination benefits in preclinical models. The combination of these drugs with chemotherapies was enhancing their activity to kill and arrest the growth of various cancer cell models. This ultimately proved to be somewhat challenging in the clinic, as these drugs generally lack tissue selectivity, so the combination of these drugs with chemotherapies in most cases was having some very toxic side-effects in patients. The side-effects limited the doses that patients were able to achieve and receive of these drugs, which in some aspects may have prevented their broader utility in the clinic. Some of the observations, however, led to explorations of these combinations that epigenetic drugs have the ability to loosen the chromatin, which could potentially make the DNA more accessible to drugs that actually target DNA itself, such as cisplatin or carboplatin.

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Epigenetic pharmaceuticals used in the clinic

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