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.