[Mioara] Cells require
energy to function, and they do that using a set
of biochemical reactions to fulfill these needs.
The sum of all these biochemical reactions forms metabolism.
However, cancer cells have no inhibition.
They evade cell death.
For that they require certain metabolic reactions
to grow and divide.
My name is Mioara Larion.
I'm a tenure track investigator leading the Cancer Metabolism Program
in the Neuro-Oncology Branch of the National Cancer Institute.
By understanding metabolism, we will be able to develop better,
less toxic anti-cancer therapeutics.
More than 80% of gliomas, which are a common brain tumor,
have a mutation in a metabolic enzyme
called isocitrate dehydrogenase 1 or IDH1.
My lab is very interested in understanding this because it's
one of the very few examples of a tumor driven
by a mutation in a metabolic gene.
We think this offers opportunity
to identify metabolic drug targets.
Cancer cells require lipids
or fats for their cellular components,
for their energy demands and for their signaling needs.
IDH1 enzyme is very important
for synthesis of these fats or lipids.
We think that brain tumors with an IDH mutation
are particularly going to be susceptible to lipid-based metabolic targeting.
We just need to understand the difference between IDH-mutated lipid metabolism
and normal cell lipid metabolism in order to identify these pathways.
My lab
employs a collection of methodologies, from standard cancer
biology techniques such as western blots and drug viability studies
to more complex techniques to study metabolism
such as mass spectrometry and Raman spectroscopy.
Very unique to our group is the ability to image and quantify
lipids using Raman spectroscopy in organelles of live cells.
This is something that sets us aside
and that enabled us to discover lipid pathways.
Besides this unique feature of our group, we also employ
more classical ways to study
metabolism, such as carbon 13 tracing analysis, in which we are able
to look at the fate of a nutrient in cancer cells and normal cells.
In 2021, we discovered that IDH1-mutated
gliomas have a unique ability to produce
more monounsaturated fatty acids,
which are a particular type of lipid
with a unique chemical structure and one double bond.
We think this is one example,
one pathway, that we can target metabolically.
We also found that in IDH-mutated glioma,
certain lipids called sphingolipids are in high abundance.
And currently we are on the way to identify
targets of the pathway specifically for IDH-mutated glioma.
My favorite part about
working in the Neuro-Oncology Branch is to see how our discoveries in the lab
are helping patients prolong their life and improve their outcome.
By understanding what lipids are good for us
and what lipids are not so good for us, we could have a better lifestyle,
a healthier lifestyle, and prevent the formation of diseases.