Team finds gene that promotes drug resistance in cancer

January 14, 2013, University of Iowa

Scientists from the University of Iowa and Brigham Young University (BYU) have identified a gene that may be a target for overcoming drug resistance in cancer. The finding could not only improve prognostic and diagnostic tools for evaluating cancer and monitoring patients' response to treatment but also could lead to new therapies directed at eradicating drug-resistant cancer cells.

is a common problem in many . It leads to failure of chemotherapy treatments and is associated with poor patient outcomes, including rapid relapse and death.

The research team, including Fenghuang (Frank) Zhan, M.D., Ph.D., and Guido Tricot, M.D., Ph.D., from the UI, and David Bearss, Ph.D., from BYU, initially focused on identifying genes linked to the development of drug resistance in , a bone marrow cancer that affects more than 20,000 Americans and causes almost 11,000 deaths annually.

Working with serial biopsied cells from 19 myeloma patients, the researchers analyzed genetic changes in the cells that occurred over the course of treatment with very intensive chemotherapy drugs. This approach identified a gene called NEK2 that is strongly associated with increased drug-resistance, faster , and poorer survival for patients. The study was published Jan. 14 in the journal Cancer Cell.

Having established the relationship between high expression of the NEK2 gene and poor patient outcome in myeloma, the team then examined the relationship in other common cancers—including breast, lung, and —by analyzing from 2,500 patients' cells with eight different cancers in Zhan's lab.

"In all cases, an increase in the NEK2 gene was associated with rapid death of the patient," says Tricot, who is director of Holden Comprehensive Cancer Center's and Myeloma Program at UI Hospitals and Clinics. "So this finding was not unique to myeloma; this is basically seen in every single cancer we looked at."

Taking the findings back to the lab, the team then examined the effect on cancer cells of either enhancing or blocking the expression of the NEK2 gene.

"Our studies show that over-expression of NEK2 in cancer cells significantly enhances the activity of drug efflux proteins to pump out of cells, resulting in drug resistance. Furthermore, silencing NEK2 in cancer cells potently decreased drug resistance, induced cell-cycle arrest, cell death, and inhibited cancer cell growth in vitro and in vivo," says Zhan, UI professor of internal medicine.

The research team is now developing compounds to inhibit NEK2 by collaborating with David Bearss, Ph.D., associate professor of physiology and developmental biology at BYU, in the hope that these compounds may overcome drug resistance in cancer cells.

"We were able to show that if we inhibit NEK2, then we can actually restore sensitivity to drugs that we use right now," Bearss says.

Although development and clinical testing of such drugs for use in patients is not imminent, Tricot notes that the findings may have clinical use within the next several years.

"NEK2 expression may be a diagnostic or prognostic marker for drug-resistant cancer," he says. "If NEK2 is high, that would suggest that the prognosis is poorer and the patient might benefit from more aggressive treatment. The other potential use is for monitoring the cancer's response to therapy. If NEK2 levels increase, that would suggest development of increased drug resistance and might indicate that a change of treatment would be helpful."

Explore further: Researchers investigate drug resistant ovarian cancer to improve clinical treatment

Related Stories

Researchers investigate drug resistant ovarian cancer to improve clinical treatment

August 9, 2012
(Medical Xpress) -- A new study by TCD researchers investigates drug-resistant ovarian cancer cells. The findings which have been recently published in the international publication, PLoS One will increase understanding of ...

Drug resistance biomarker could improve cancer treatment

November 21, 2012
Cancer therapies often have short-lived benefits due to the emergence of genetic mutations that cause drug resistance. A key gene that determines resistance to a range of cancer drugs has been reported in a study published ...

Possible new therapy for the treatment of myeloma

September 5, 2012
(Medical Xpress)—Research from Karolinska Institutet shows that sorafenib, a drug used for advanced cancer of the kidneys and liver, could also be effective against multiple myeloma. The disease is one of the more common ...

Computational analysis identifies drugs to treat drug-resistant breast cancer

July 31, 2012
Researchers have used computational analysis to identify a new Achilles heel for the treatment of drug-resistant breast cancer. The results, which are published in Molecular Systems Biology, reveal that the disruption of ...

Researchers use new tool to counter multiple myeloma drug resistance

September 9, 2011
Moffitt Cancer Center researchers, and colleagues, are pioneering promising research utilizing a monitoring technology that could provide a better understanding of acquired drug resistance and assist in clinical decision-making ...

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.