Researchers aim to over-stress already taxed mantle cell lymp...( AUGUSTA Ga. - Cancer cells are alrea...),Health

AUGUSTA, Ga. - Cancer cells are already stressed by the fast pace they require to grow and spread and scientists believe a little more stress just may kill them.

"Think about an assembly line in a factory that is working five times faster than normal," said Dr. Kapil Bhalla, director of the Medical College of Georgia Cancer Center. "There is a lot of stress but you need workers to keep going. Some of them fall out, some get bent out of shape."

His research team believes they can disrupt the over-stressed assembly line of mantle cell lymphoma and possibly similar cancers such as pancreatic, liver and breast, by taking away support needed for rapid protein turnover and by clogging up the mechanism for eliminating poorly made ones.

Mantle cell lymphoma, an aggressive cancer of the lymphatic system that mostly occurs in middle age, responds initially to chemotherapy and antibiotics, but often returns, said Dr. Bhalla. Patients have a median survival of three to four years. This cancer affects b lymphocytes, immune cells which make antibodies to fight infection. Ironically, in the process of rearranging genes to make antibodies to a specific invader, mistakes happen, and a would-be protector becomes cancer.

MCG researchers found that to keep their fast pace, these now-malignant cells need increased activity of heat shock protein 90. "Cancer cells require hsp90 for keeping their proteins in active conformation to do their job. That is what cancer is addicted to," said Dr. Bhalla, Cecil F. Whitaker, Jr., M.D./Georgia Research Alliance Eminent Scholar in Cancer and Georgia Cancer Coalition Distinguished Cancer Scholar. Hsp90 is one of the more common molecular chaperones, which help proteins get made, moved, folded and function. Its levels and activity are upregulated in response to stress.

They also found that the usually busy endoplasmic reticulum of these cells, which is supposed to be making normal antibodies, is
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