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.
Drug resistance is a common problem in many metastatic cancers. 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 multiple myeloma, 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 cancer growth, 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 bladder cancer -- by analyzing gene expression profiles 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 Bone Marrow Transplant and Myeloma Program at UI Hospitals and Clinics. "So this finding was not
|Contact: Jennifer Brown|
University of Iowa Health Care