Experimental Treatment Targets Genetic Mutation

Kambra McConnel ([email protected]) (310) 206-3769

EXPERIMENTAL TREATMENT AT UCLA'S JONSSON CANCER CENTER TARGETS A GENETIC MUTATION FOUND IN 90 PERCENT OF

PANCREATIC CANCER CASES

Researchers at UCLA's Jonsson Cancer Center today (Feb. 22) began a new experimental treatment that targets a genetic mutation found in about 90 percent of pancreatic cancer cases. UCLA is the only site in Southern California to offer the new therapy.

Doctors are seeking volunteers with pancreatic cancer to participate in the study, which targets a growth-stimulating protein produced by a cancer-causing gene called ras. The gene plays a role in the development of many types of cancer, including pancreatic cancer, said Dr. Rafael Amado of UCLA's Jonsson Cancer Center, the principal investigator in the study.

Laboratory studies suggest that a protein from mutated ras genes may play a central role in the development of cancer, signaling cells to divide out of control, Amado said. In the new study at UCLA, researchers hope to inhibit the ras signaling in humans, causing their tumors to regress, or shrink.

The study will randomly assign participants into two groups. One will take the experimental drug SCH66336 created by the Schering-Plough Research Institute, while the other group receives Gemcitabine, a standard chemotherapy used against pancreatic cancer. Patients taking the Schering-Plough drug must swallow two capsules twice a day for 28 days and undergo blood tests weekly, said Dr. Lee Rosen, co-investigator in the study.

Amado and Rosen are optimistic about the experimental therapy, which attempts to control what is broken in a cancer cell.

"This is targeted therapy," Amado said. "It's the first compound used against pancreatic cancer that tries to address one of the fundamental biological problems with the disease. This biochemical molecule gets into the cells and prevents ras from undergoing an essential modification it needs to become active."

Simply put, the protein from the ras gene acts like an electrical switch in a signaling sequence that regulates cell division. A mutation in the gene causes this switch to stick in the "on" position, contributing to uncontrolled cell division, possibly leading to cancer. Amado hopes the new drug, which acts as a farnesyl transferase inhibitor, will stop the mutated ras protein from signaling the cell to divide, restoring the switch to the "off" position.

In laboratory models, farnesyl transferase inhibitors induce programmed cell death, a process called apoptosis. Amado hopes that cancer cells carrying ras mutations will undergo programmed cell death after exposure to this new drug.

"In the laboratory, this drug induced regression in tumors with ras mutations," Amado said.

In 1998, pancreatic cancer struck 29,000 people in the United States, according to the American Cancer Society. It was fatal in more than 99 percent of cases.

"With the standard care for pancreatic cancer, results are very poor," Amado said. "Anyone with advanced disease should consider participating in experimental treatments such as this, which are based on promising preclinical results."

The drug has proved safe for humans in Phase I trials. This Phase II trial will determine how effective it is against pancreatic cancer. Worldwide, 60 patients will participate in the study at 30 sites, including UCLA's Jonsson Cancer Center.

Patients with untreated, advanced pancreatic cancer, either newly diagnosed or recurrent, are eligible to participate in the study. Patients must undergo routine scans and blood tests to determine the extent of their disease. Possible side effects include fatigue, nausea, abdominal discomfort, weight loss, anemia and reversible kidney dysfunction.

"This represents a new class of drugs that will be very important in the future of cancer treatment," said Rosen, who directs the UCLA's Cancer Therapy Development Program. "We're hopeful that this may represent a new way to treat pancreatic cancer."

For more information on the UCLA study, call (310) 825-8375.

-UCLA-

For more information about UCLA's Jonsson Cancer Center, its people and resources, visit our site on the World Wide Web at http://www.cancer.mednet.ucla.edu