Nature solves a long-standing mystery about how cancer-promoting proteins lead to drug-resistant tumor growth

Scientists have solved a long-standing mystery about a cancer-promoting protein and how it causes tumor growth
.
Because aggressive tumors tend to develop resistance to drugs and other treatments, these findings are an important step in
exploring ways to improve the efficacy of cancer drugs.

A recent team of University of Utah researchers studied a protein called Smoothened, which plays a vital role
in healthy tissue and organ development.
However, when Smoothened is overactive, it triggers the formation and spread
of brain and skin tumors.
Blocking Smoothened can stop the cancer from spreading, but eventually the tumor adapts, making this approach ineffective
.
Medulloblastoma is the most common childhood brain tumor in the United States, while basal cell carcinoma is the most common cancer in the United States, with about 3.
6 million cases per
year.

"Our findings suggest that we can use some new strategies in the clinic to improve patient outcomes
," Myers said.

Smoothened is part of
a signaling pathway in the body.
The signaling pathway is like a telephone line
from the cell surface to the inside of the cell.
The information transmitted along this line provides instructions
to the cell.

"We knew the 'phone line' existed, but we didn't know how it worked
.
This leaves a big gap
in our ability to turn it off when treating cancer.
"Hopefully, by better understanding it, cancer drugs will become more effective
.
"

These findings explain how Smoothened is activated at the molecular level and what the signals are
transmitted.

Myers said biology undergraduates working in his lab were crucial
to the discovery.
He also wanted to thank key interns John Happ, Corvin Arveseth and Isaac Nelson, as well as postdoctoral students
who were crucial to his research.
Key collaborators include Dr.
Susan Taylor of the University of California, San Diego, Dr.
Friedrich Herberg of the University of Kassel, Germany, and Dr.
Gianluigi Veglia of the University of Minnesota.

The study was supported
by the National Institutes of Health and the Huntsman Cancer Foundation.