DEC 17, 2016 8:47 AM PST

Deficiency of Two Opposing Enzymes Spurs Liver Cancer

WRITTEN BY: Xuan Pham

If a cancer is caused by the over-activation of proteins that enhance growth, then blocking these enzymes should stunt the tumor. Yet, in liver cancer, drugs that inhibit growth enzymes do not seem to slow the cancer growth. And the most recent research suggests that cancer biology is more complex than previously thought.

"When it comes to liver cancer, I think we've been making strategic mistakes," said Gen-Sheng Feng, professor at the University of California, San Diego, and the study’s senior author. "In cancer development, we always thought about two distinct families of enzymes -- one promotes cancer, one inhibits it.”

Indeed, this line of thinking has led to the creation of drugs that, for the most part, do one or the other. That is, they either block the over-active pro-cancer enzymes or stimulate the activity of anti-cancer proteins. “Many drugs have been developed to block the cancer-promoting pathways, but we and others are now finding that many classical pro-cancer proteins are actually inhibitors,” said Feng. This explains why the intended consequences for anticancer drugs don't always work.

To better understand the mechanism behind why cancer drugs fail in liver cancer, the team honed in on the balance of tumor-suppressor genes versus those that promote tumor growth in a mouse model. They found that mice that lacked both types of proteins are, paradoxically, most susceptible to liver disease and cancer.

In particular, the two opposing cancer proteins were identified as Shp2 and Pten. Shp2 is well-characterized as a tumor-promoting protein, while Pten is a known tumor-suppressing protein. Yet, mice with a loss of both of these proteins had the largest and most prominent tumor formation in the shortest amount of time.

"So the roles of tumor-promoting and tumor-suppressing enzymes are not as simple as we thought," Feng said. "This also explains many unwanted side effects with drugs that target these enzymes. Their consequences can differ depending on cell type."

Feng’s team theorized that loss of the two enzymes triggered uncontrolled inflammation and fibrosis in the liver, which helped promote tumor formation. Interestingly, when they analyzed human liver cancer samples, the team found a similar pattern – those with low or deficient levels of SHP2 and PTEN typically had the poorer prognoses.

"Liver cancer is more complicated than we thought. These pathways, when over-activated, stimulate tumor development, but so does inhibiting them," Feng said. "That's why we can't rush to conclusions like we have in the past. But now that we have a good model that mimics the human pathogenic process and we can use that to work out the mechanisms that lead to liver disease and cancer, and search for novel drug targets."

Additional sources: UC San Diego Health

About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
You May Also Like
NOV 29, 2019
Immunology
NOV 29, 2019
Protecting Killer Immune Cells from Themselves
Destroying human cells compromised by viruses and cancer is the name of the game for so-called “killer” cells of the immune system. They employ...
DEC 08, 2019
Cancer
DEC 08, 2019
Is there an association between smoking marijuana and cancer?
The controversy with marijuana is only likely to continue as research studies try to understand if marijuana use is associated to an increased risk of canc...
DEC 09, 2019
Cancer
DEC 09, 2019
Hair dyes associated with increased risk of breast cancer
Research recently published in the International Journal of Cancer suggests that certain hair dyes and chemical relaxants are associated with breast cancer...
JAN 08, 2020
Health & Medicine
JAN 08, 2020
Cancer Death Rates Declining in U.S., According to New Report
In the United States, the death rate from cancer has declined, according to a new report released today by the American Cancer Society. The video below sum...
JAN 09, 2020
Drug Discovery & Development
JAN 09, 2020
Can Cancer Drugs Treat Lung Damage?
Can therapeutics used in the treatment of cancer be a breakthrough for pulmonary disease? Specifically, chronic obstructive pulmonary disease (COPD)? &ldqu...
JAN 15, 2020
Cancer
JAN 15, 2020
Hope for patients with AML
Research published recently in the medical journal EMBO Molecular Medicine brings hope for leukemia patients with a report that a common and cheap drug may...
Loading Comments...