Strategies for Combating Cancers

The researchers who followed Ames and Willett focused on the impact of biotechnology on diseases that might once have led clinicians to offer their patients little hope.

Ramesh Shivdasani, Assistant Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School, described the use of a Novartis drug, Gleevac, in treating patients with chronic myeloid leukemia (CML).

The drug targets a cancer-triggering protein created by the switching of genes between chromosomes 9 and 22.

"This disease is associated with a chromosome translocation in that region of the genome and that resulted in the activation of disease progression," said Shivdasani, who receives some funds from Novartis. "The origins of Gleevac rest on the understanding of disease at the most fundamental level."

Scientists have learned from such successes that clues to possible treatments can be found in the cells of patients, and that the search for solutions must be carried out "as a confluence of many different fields."

"The time line for Gleevac was almost two decades," Shivdasani said. "But the lesson is that if the work is well grounded in science, the pay off will continue to be very large…We hope that approaches such as this may help in the intervention of other diseases."

Steven Rosenberg, Chief of Surgery at the National Cancer Institute, pioneered development of successful immunotherapy treatment of selected patients with advanced cancers, and was the first to insert foreign genes into humans. His article on a possible cancer therapy that shrinks melanoma tumors appeared in ScienceExpress on 19 September 2002. Since then, he told the audience yesterday, the method has continued to prove effective among most of the patients in the trial, which has expanded from 13 patients to 27.

"We take advantage of the body's response to cancer, and we have made considerable progress" Rosenberg said, in explaining his team's approach to cancer treatment.

Rosenberg and his colleagues removed T cells from patients' bodies, chose the ones that seemed most successful in attacking tumor cells, and re-inserted them in the body. The experiment did not work initially, as the T cells seemed to disappear shortly after insertion. In the end, the scientists decided to suppress the subjects' immune systems, and to pair the CD 8 cells they had been using with CD 4, or helper T cells. The strategy worked, and 10 out of 13 patients saw their melanoma tumors shrink dramatically.

During treatment, natural brakes were taken off the T cells to boost their response to the antigens on the surface of the tumor cells. As a result, Rosenberg said, several of the patients developed auto-immune diseases, although they were successfully treated with steroids.

"The immune system is poised to destroy every organ in our body," Rosenberg said. "We live in this delicate balance. The research demonstrated that this regulatory mechanism can be affected."

—Coimbra Sirica

15 October 2003

Read related article from Advancing Science Seminar on Prevention of Chronic Disease.