Colon cancer is the third most common type of cancer in men and
women and the second leading cause of cancer-related mortality in the
United States, suggests the National
A small molecule called TASIN-1 can selectively kill cells with a
mutation that is considered to be a precursor to colon cancer, while
sparing related normal cells, UT Southwestern Medical Center cancer
biologists have demonstrated. The mutated cells that are killed using
TASIN-1 are found in more than 80% of colon tumors.
The findings could eventually help with both prevention and
intervention efforts for colon cancer.
‘A small molecule called TASIN-1 can selectively kill cells with a mutation that is considered to be a precursor to colon cancer, while sparing related normal cells.’
"Even though such mutations are common in colorectal cancer, there
are currently not any therapeutics that directly target these types of
mutations, so this represents fresh avenues to approach," said Dr. Jerry
Shay, Professor of Cell Biology and a member of the Harold C. Simmons
Comprehensive Cancer Center at UT Southwestern. "Our latest finding
confirms that targeting TASINs is a viable approach."
Using specifically engineered human colonic epithelial cells,
researchers were able to screen over 200,000 small molecules using the
high throughput screening core to identify TASIN-1 (truncated APC
selective inhibitor). TASIN-1 is a small molecule that selectively kills
cells that have a mutation in a gene called APC, or adenomatous
polyposis coli. APC is a gene that suppresses the formation of tumors.
TASIN-1 specifically kills cells with the mutated/truncated APC, but
spares normal and cancer cells with the standard full length APC.
"Considering the high prevalence of APC mutations in colon cancer
patients, targeting truncated APC could be an effective therapeutic
strategy for prevention and intervention of colorectal cancer and could
potentially be used as a marker for stratifying patients in future
personalized medicine clinical trials," said Dr. Shay, The Southland
Financial Corporation Distinguished Chair in Geriatrics.
After demonstrating the concept worked on cells, researchers from
the Shay/Wright lab and colleagues were able to confirm the results in
genetically engineered mouse models that a susceptible to colon cancer
as well. The research appears in Science Translational Medicine