Researchers at Texas A&M University have identified the enzymes that switch on a little-understood stress-protection system in human cells, a system that may help some cancer cells survive chemotherapy. In lab experiments, blocking the pathway with an experimental drug, pevonedistat, alongside the chemotherapy drug cisplatin killed liver cancer cells more effectively than either treatment alone, the university reported.
The research was published in Nature Communications in April and publicized by the university on September 23. It targets one of the most frustrating problems in cancer care: tumors that survive treatment. The results come from cell experiments, not patients, and they do not change how liver cancer is treated today.
Mapping a Little-Known Cellular Shield
The team, led by Wenshe Liu, PhD, a Regents Professor at Texas A&M, studied a protein called URM1 that has been preserved across species for hundreds of millions of years. Scientists knew it helps cells respond to stress, but no one had identified the enzymes that activate it in human cells. The researchers designed a molecular probe to capture proteins involved in URM1 activity.
That probe pointed to two enzymes, NAE1/UBA3 and UBE2M. Disrupting either one sharply reduced URM1 activity, and compounds that block the enzymes had the same effect. The team also found that oxidative stress, a type of cell damage caused by normal metabolism and by many cancer drugs, strongly activates URM1, which appears to help protect cells against that stress.
Many cancer drugs work by overwhelming tumor cells with this kind of damage. "We still have much to learn about which proteins are controlled by URM1 and how that influences disease," Liu said, adding that identifying the key enzymes gives researchers a clearer roadmap, Medical Xpress reported.
Cell Experiments, Not Treatment Advice
This is laboratory research in cells, published in a peer-reviewed journal. The study also found that high URM1 levels were associated with poorer outcomes in liver cancer patients, but an association does not show that the protein causes worse survival. Any benefit of targeting the pathway in patients remains untested.
Pevonedistat also carries a caution. It is an investigational drug that has not been approved by the FDA, and a large Phase 3 trial of it in blood cancers did not meet its main goal in 2021. A drug that falls short in one cancer can still be studied in another, but the new lab data do not show it would help people with liver cancer.
Liver Cancer Patients and the Road Ahead
Liver cancer is a growing concern in the United States. The American Cancer Society estimates about 42,340 new cases of primary liver and intrahepatic bile duct cancer and 30,980 deaths in 2026, and incidence rates have tripled over the past four decades. National SEER data track how often these cancers are diagnosed over a lifetime. Worldwide, more than 800,000 people are diagnosed each year, and the disease is far more common in sub-Saharan Africa and Southeast Asia than in the United States.
People at higher risk include those with chronic hepatitis B or C, cirrhosis, heavy alcohol use, or fatty liver disease linked to excess weight and diabetes. Early liver cancer often causes no symptoms. Later signs can include unexplained weight loss, pain or swelling in the upper abdomen, and yellowing of the skin or eyes, which should prompt a medical visit.
Patients receiving chemotherapy should not seek pevonedistat or other experimental drugs outside a clinical trial and should not stop prescribed treatment without talking to their oncologist. People at high risk can ask a clinician whether regular liver cancer surveillance is recommended for them. Hepatitis B vaccination and hepatitis C treatment remain proven ways to lower risk.
The researchers say more work is needed to learn how the pathway functions in patients and whether it can be targeted safely. Studies in animals and in patient tumor samples would likely come long before any patient trial. For now, the study is useful science to follow with measured expectations.
Key Questions Answered
What did Texas A&M researchers find? They identified two enzymes that activate the URM1 stress-protection pathway in human cells. Blocking the pathway made liver cancer cells more vulnerable to cisplatin in lab tests.
Was the research done in patients? No. The experiments used cells in the lab.
What is pevonedistat? It is an investigational drug that blocks NAE1/UBA3. It is not FDA-approved and did not meet its main goal in a 2021 blood cancer trial.
Does high URM1 cause worse outcomes? That is not proven. The study found an association between high URM1 levels and poorer outcomes in liver cancer patients.
Should patients change their chemotherapy? No. Do not change or stop treatment without talking to an oncologist.
Who is at higher risk of liver cancer? People with chronic hepatitis B or C, cirrhosis, heavy alcohol use, or fatty liver disease. A clinician can advise on surveillance.
Published by Medicaldaily.com
