UTSW University. US: UT Southwestern Medical Center researchers seeking novel ways to combat
cancer found that giving acetate, a major compound produced in the gut
by host bacteria, to mice sped up the growth and metastasis of tumors.
Bacteria living inside the gut can have beneficial, but potentially
also harmful effects on human health. Further studies are needed to
determine whether restricting acetate production by gut bacteria will
affect growth of tumors.
“With insights generated from our current studies, we may be able to
design therapies that treat cancer patients by modulating acetate
production in the body,” said Dr. Joseph Garcia,
Associate Professor of Internal Medicine at UT Southwestern and staff
physician-scientist at the VA North Texas Health Care System.
The work is published in the February issue of the journal PLoS ONE.
Cancer, the second leading cause of death in the US, is estimated to
account for nearly 1 out of every 4 deaths in 2014. It can have a
significant impact on length and quality of life, which carries a
tremendous economic burden. Cancer can develop in any part of the body
and some are notoriously difficult to treat, although recent discoveries
from basic science laboratories hold great promise for more effective
treatments and potential cures.
In cancer cells, low oxygen and low glucose conditions turn on
signaling pathways that allow otherwise healthy cells to survive these
stresses. UT Southwestern researchers previously discovered a critical
pathway that controls the response of cells and organs to low oxygen
conditions, a state known as hypoxia. In this study, the researchers
show that the production of acetate is also stimulated by low glucose
conditions, another condition frequently found in solid tumors.
Acetate, in turn, activates a molecular pathway that ultimately
results in the production of several proteins that stimulate the growth
and spread of tumors.
“Our study shows that acetate functions in this context as a growth
signal for cancer cells, one that links changes in metabolism within
cancer cells that occur during tumor growth with activation of a
selective stress-signaling pathway. This same signaling pathway is
normally protective in healthy individuals. In fact, stimulating this
pathway in anemic mice without cancer has a profound effect on restoring
red blood cell levels to near-normal or normal levels, and is otherwise
very safe” said Dr. Garcia, a member of the Harold C. Simmons
Comprehensive Cancer Center.
“The challenge facing us now is to define which patients may benefit
from having this pathway stimulated and which patients will benefit from
having this pathway inhibited. Preclinical studies of this nature are
essential for informing the pharmaceutical and federal health oversight
agencies about potential benefits as well as potential harms that may
result from use of compounds that affect this key signaling pathway,”
said Dr. Garcia.
Other researchers involved in the work include Dr. Robert D. Gerard,
Associate Professor of Molecular Biology; Min Xu, Research Scientist;
Jason Nagati, Research Assistant; researchers Alok Das and Richard Hogg;
and Dr. Rui Chen, former Assistant Professor of Internal Medicine.
The research was supported by funds provided by the Department of Veterans Affairs and the National Institutes of Health.
UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center
is one of just 68 NCI-designated cancer centers in the nation. The
Simmons Cancer Center includes 13 major cancer care programs with a
focus on treating the whole patient with innovative treatments, while
fostering groundbreaking basic research that has the potential to
improve patient care and prevention of cancer worldwide. In addition,
the Center’s education and training programs support and develop the
next generation of cancer researchers and clinicians.
In addition, the Simmons Cancer Center is among only 30 U.S. cancer
research centers to be named a National Clinical Trials Network Lead
Academic Participating Site, a prestigious new designation by the NCI,
and the only Cancer Center in North Texas to be so designated. The
designation and associated funding is designed to bolster the cancer
center’s clinical cancer research for adults and to provide patients
access to cancer research trials sponsored by the NCI, where promising
new drugs often are tested.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the
nation, integrates pioneering biomedical research with exceptional
clinical care and education. The institution’s faculty includes many
distinguished members, including six who have been awarded Nobel Prizes
since 1985. Numbering more than 2,700, the faculty is responsible for
groundbreaking medical advances and is committed to translating
science-driven research quickly to new clinical treatments.
UT Southwestern physicians provide medical care in 40 specialties to
nearly 91,000 hospitalized patients and oversee more than 2 million
outpatient visits a year.