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Dr. Caudle:
Currently, molecular subtyping
serves primarily a predictive, prognostic
purpose in gliomas. One study presented
here actually revealed that targetable
fusions were found via RNA sequencing
and up to 10% of astrocytomas. Another
study demonstrated clinical activity of
vemurafenib in BRAF mutant gliomas. So
do you foresee targeted therapies playing
a role, an important role rather in managing
gliomas in the future? And if so, which other
genes or mutations do you predict will be
the most attractive or useful candidates?
Dr. Wick:
Yeah. I think it’s important, very
important topic. So we have to look at gli-
omas as a bunch of disease. It’s not just
one disease. There are gliomas, and the
BRAF-mutated xanthoastrocytoma is a very
nice example, that are driven primarily by
a single lesion or at least in a single path-
way. Pilocytic astrocytoma, pleomorphic
xanthoastrocytoma, and probably also a
few others are really dependent on the
BRAF and MEC pathway. And therefore, in
that disease, these inhibitors will be effec-
tive. We don’t know how fast resistance
is evolving, but they will be effective and
we’ve seen that. So patients are not only
stabilized over a prolonged period of time,
but the tumor tissues actually responding
to the treatment. So cells are dying, cells
are going away with that treatment. So this
is important.
Dr. Caudle:
Yes.
Dr. Wick:
Second, if you are looking at the
broader scope of gliomas, this is a very
heterogeneous disease. So what we
need to define is what are really the driv-
ing alterations in that disease. We look at
IDH mutations, so the mutated isocitrate
dehydrogenase where several compa-
nies are now building inhibitors. There will
be glioma patients benefiting from that
approach. I think this is for sure. There are
a lot of patients harboring a TERT mutation,
a certain telomerase activating alteration,
which is also something which is very high
up in the hierarchy of the alterations in
the tumor tissue and therefore may be an
attractive target.
There are other alterations like all the EGF
receptor alterations, which play a big role
in lung disease, other cancers. They are
only in the minority of tumor cell subclones
and therefore probably only 20% to 25%
of cells in a given patient are responding
and this is not perfect alterations. Coming
to that abstract, I think fusions are an over-
looked molecular entity in gliomas. So it’s a
very attractive target. We understand that
those fusions need to be assessed with
the genetics that we are doing. We were
focusing on the axon. We are doing that.
We will miss the fusion, so RNA sequencing
is something we should look for. There are
certain panels, also DNA panels that are
already integrating the fusions and several
of those fusions are and will be assessable
for treatments in the future. I’m pretty confi-
dent that we will have more drugs targeting
those fusions and then get some benefit, at
least in selected patients from it.
Dr. Caudle:
Right. Right. That makes sense.
And you know, sort of, I think we mentioned
a little bit about hopes for the future, you
know, let’s talk about maybe the past year.
What do you feel is the most significant
advance in managing CNS malignan-
cies over the past year and what do you
see as some of the most promising treat-
ments or therapeutics that are currently in
development?
Dr. Wick:
So let’s start probably with a very
conceptual point.
Dr. Caudle:
Okay.
Dr. Wick:
I think we are now on this turning
point of really better understanding the
Emerging Science
in Gliomas and
Glioblastomas: A Review
Interview with Wolfgang Wick
MD
by Jennifer N. Caudle
DO
Dr. Wick is Division Head of Neuro-Oncology at
the German Cancer Research Center (DKFZ),
Program Chair of Neuro-Oncology at the
National Center for Tumor Diseases (NCT), and
Professor of Neurology and Chairman at the
Neurology Clinic in Heidelberg, Germany.
I think fusions are an overlooked molecular entity in gliomas.
So it’s a very attractive target. We understand that those fusions
need to be assessed with the genetics that we are doing. We were
focusing on the axon. We are doing that. We will miss the fusion,
so RNA sequencing is something we should look for.
Q & A
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