Cancer's hidden vulnerabilities

Date:
September 28, 2020
Source:
California Institute of Technology
Summary:
To fight cancer more effectively, a researcher probes its inner
workings for metabolic weaknesses.



FULL STORY ==========================================================================
One of the biggest challenges to the development of medical treatments
for cancer is the fact that there is no single kind of cancer. Cancers
derive from many kinds of cells and tissues, and each have their own characteristics, behaviors, and susceptibilities to anti-cancer drugs. A treatment that works on colon cancer might have little to no effect on
lung cancer, for example.


==========================================================================
So, to create effective treatments for a cancer, scientists seek
insight into what make its cells tick. In a new paper appearing in Nature Communications, Caltech researchers show that a framework they developed,
using a specialized type of microscopy, allows them to probe the metabolic processes inside cancer cells.

The work was conducted by researchers from the laboratory of Lu Wei,
assistant professor of chemistry, as well as from the Institute for
Systems Biology in Seattle and UCLA. It utilizes a technique called
Raman spectroscopy in conjunction with its advanced version, stimulated
Raman scattering (SRS) microscopy. Raman spectroscopy takes advantage of
the natural vibrations that occur in the bonds between the atoms that
make up a molecule. In this method, a molecule is bombarded with laser
light. As the laser light's photons bounce off the molecule, they gain
or lose energy as a result of their interaction with the vibrations in
the molecule's bonds. Because each kind of bond in a molecule affects
photons in a unique and predictable way, the structure of the molecule
can be deduced by how the photons "look" after they bounce off of it. By mapping the distribution of targeted chemical bonds, SRS microscopy then provides imagery of these molecular structures.

Using those combined techniques, Wei and her fellow researchers examined
the metabolites present in five cell lines of melanoma commonly used
in research.

The melanoma cells were chosen, according to Wei, because they have a
wide spectrum of metabolic characteristics that can be studied.

By studying the cells' metabolites, the researchers can begin to deduce
how their metabolisms work, and how they could be targeted by drugs. This
is similar to how a saboteur might gather information about the machinery
in a factory in order to plan where they can cause the most damage.

"The question we are interested in is why all the cancer cells we look
at have very different behaviors," Wei says. "Because some cells have
higher reliance on some metabolic pathways, they are more susceptible
to disruption of those pathways." Wei says the team uncovered a few
new metabolic susceptibilities in cancer cells, including fatty acid
synthesis and mono-unsaturation, but adds that right now, the primary
purpose of the research is to do fundamental science.

"We've introduced a framework of pushing Raman spectroscopy into systems biology," she says. "And we're using sub-cellular information we've
gathered with it to guide our study into pharmacometabolomics -- the
study of how metabolism affects drugs." James R. Heath of the Institute
for Systems Biology in Seattle and co-author on the paper says this
new technology allows researchers to obtain a more detailed look inside
cancer cells than ever before.

"The chemical imaging methods developed in Lu's lab allowed us to
identify druggable metabolic susceptibilities in some very aggressive
cancer models.

These metabolic weaknesses would be missed by any other analytical
approach," Heath says.


========================================================================== Story Source: Materials provided by
California_Institute_of_Technology. Original written by Emily
Velasco. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jiajun Du, Yapeng Su, Chenxi Qian, Dan Yuan, Kun Miao, Dongkwan Lee,
Alphonsus H. C. Ng, Reto S. Wijker, Antoni Ribas, Raphael
D. Levine, James R. Heath, Lu Wei. Raman-guided subcellular
pharmaco-metabolomics for metastatic melanoma cells. Nature
Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-18376-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200928093744.htm

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