[UTA Magazine]


Coping with cancer treatments
Ground-breaking research aims to make chemotherapy and radiation more tolerable

Chemotherapy and radiation treatments have aided recovering cancer patients for years, but the side effects can be agonizing. Thanks to a study headed by Sanjay Awasthi, a UTA biochemistry research professor, these treatments may not be so debilitating in the future.

Dr. Awasthi and his project team, which includes Sharad Singhal, a UTA biochemistry research assistant professor, recently discovered that RLIP76, a gene previously cloned with unknown function, is a protein that transports anti-cancer drugs out of the cancer cells.

Sanjay Awasthi and Sharad Singhal
Biochemistry faculty members Sanjay Awasthi and Sharad Singhal are researching methods that cause cell death in lung and other cancers.

“RLIP76 protects the cells from radiation and from chemotherapy,” Dr. Awasthi said. “It is thus a mechanism that cancer cells use to protect themselves from chemotherapy. We have developed methods to inhibit this protein in cancer cells and have shown that inhibiting this protein causes cell death in lung and other cancers in cell culture.”

The team has developed liposomes to deliver RLIP76 to normal cells, like those in the esophagus and skin, to protect them from collateral damage from radiation and chemotherapy. The researchers hope to develop these liposomes—microscopic, fluid-filled pouches used to deliver drugs to the body—for use in cancer patients to protect normal tissue and make it easier for patients to cope with treatment.

The manner in which chemotherapy kills rapidly dividing cancer cells also causes it to kill healthy cells like the membranes lining the mouth, the lining of the gastrointestinal tract, hair follicles and bone marrow. The side effects of chemotherapy can be traumatic in these areas.

“Our research is directed at defining the causes of chemotherapy and radiation resistance in lung cancer,” Dr. Singhal said. “Our studies in lung cancer cells have led us to a novel finding that RLIP76 is a chemotherapy drug transport protein capable of mediating resistance not only to chemotherapy agents, but also to radiation.”

Dr. Awasthi has been working on this study since he was 14. His father, Dr. Yogesh Awasthi, was researching a similar problem when young Sanjay became interested in the project.

“I went off to college and to medical school and residency and worked on it on and off from about 1985,” he recalled. “A paper was published in 1987 stating that there was a process like this, but no one knew exactly what it was.”

Since then, Dr. Awasthi, an M.D. with an oncology/ hematology practice at the Texas Cancer Center in Arlington, has published almost 100 papers on the subject.

In addition to Drs. Awasthi and Singhal, the team includes Yogesh Awasthi and Dr. Rajendra Sharma, both from The University of Texas Medical Branch at Galveston, and Dr. Piotr Zimniak of the University of Arkansas for Medical Sciences in Little Rock.

Their work is drawing international attention. They were featured on the cover of the Sept. 20 International Journal of Cancer and have been acknowledged in the International Journal of Oncology and several other publications.

“It’s nice that they recognize us in this way,” Dr. Awasthi said.

The research is funded by a grant from the National Institutes of Health. The program is expected to cost more than $800,000 for the next five years, and the team has applied for additional funding from the North Texas Cancer Research Foundation and the NIH.

Faculty research associate Sushma Yadav, who’s working on a postdoctoral fellowship in biochemistry, is optimistic about the results.

“We can make chemotherapy more effective,” she said. “We can give the protein to cancer patients before radiation to protect the organs.”

The news should one day have lung cancer patients breathing a little easier.  

– Jim Patterson

Online: www3.interscience.wiley.com

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