Fox Chase Cancer Center Studies Breast Cancer Drug Made from "Sea Squirts"
PHILADELPHIA (October 22, 2002) -- Cancer researchers around the world, including those at Fox Chase Cancer Center, hope a drug made by a small sea creature can help treat cancer. The agent is found in the tissues of a common ocean-dwelling animal called a sea squirt, or "Ecteinascidia turbinata," by its scientific name. One substance derived from it is called ET-743 (Yondelis�), studied clinically since the late 1990s.
ET-743 has been studied in European and American clinical trials for the treatment of soft-tissue sarcomas. Soft-tissue sarcomas are less common cancers affecting blood vessels, muscles, tendons, and other connective tissues. Now, researchers at Fox Chase and elsewhere want to know if ET-743 will be effective in treating more common cancers, including advanced breast cancer.
"Breast cancer, when caught early, often can be successfully treated, but fewer treatment options exist for women whose cancer has spread," said Lori J. Goldstein, M.D., director of the breast evaluation center at Fox Chase and principal investigator for the latest ET-743 study. "Since the beginning of time, we have turned to nature to find medicinal agents. This time, we're looking to the sea with hopes that the sea squirt drug can help us treat advanced breast cancer."
Researchers have described a number of ways by which ET-743 might fight cancerous growth. Kathleen Scotto, Ph.D., a member of the Fox Chase Cancer Center pharmacology department, has spent several years researching the active mechanisms of ET-743.
"It is believed that ET-743 prevents cells from multiplying and selectively causes the cancer cell to die," explained Scotto. "How the drug accomplishes this is not yet clear, but we have shown that ET-743 is a novel and potent inhibitor of activation of a subset of genes that may be involved in the life and death decision made within a cell."
The safety of ET-743 has been tested in several Phase I clinical trials and additional studies continue. Roger B. Cohen, M.D., director of Phase I clinical trials at Fox Chase, is conducting two Phase I clinical trials using ET-743 for solid tumors. Phase I studies are the first step in testing a new treatment where the drug is tested for safety. In addition, Goldstein is the principal investigator of a Phase II trial (third-line therapy) for breast cancer, the second step in the drug approval process. Phase II studies determine how well a drug works.
From Sea to Seashore
"Sea squirts get their name from their tendency to squirt out water when gentle pressure is applied to their sac-like bodies after they are removed from their watery home," said Dominique Didier Dagit, Ph.D., Associate Curator of Ichthyology at the Academy of Natural Sciences in Philadelphia.
"The sea squirt body basically consists of a sac, that may range from the size of a grape to the size of your fist, with two openings. One allows water to flow into the round body, while the other tube squirts the water out after filtering nutrients. Sea squirts attach themselves to the sea floor or to rocks, sometimes by a long stalk, and usually remain in one place their entire lives," Dagit added.
Kenneth Rinehart, Ph.D., emeritus professor of chemistry at the University of Illinois, was the first to isolate the compound now known as ET-743 (ecteinascidin) from sea squirts in the late 1980s. PharmaMar, a Spanish company, is developing the drug as a cancer treatment and is seeking approval to market it in Europe. In an agreement with PharmaMar, Ortho Biotech Products, L.P., a Johnson & Johnson company, licensed the drug for potential sale outside of Europe, including the United States.
ET-743 is a powerful substance. Less than an ounce is enough to treat dozens of patients. Sea squirts grow abundantly in clusters in all the world's oceans, including the Mediterranean and Caribbean seas. The tube-like creatures can also be farmed. In Japan, sea squirts are considered a culinary delicacy.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., is sponsoring Fox Chase Cancer Center's Phase II clinical trial of the sea squirt drug for advanced breast cancer; however, it will take several years of human testing to obtain U.S. government approval.
If Phase II studies show promising results, the drug would be tested in hundreds of patients as part of a Phase III trial, which compares new drugs to standard treatments. The Food and Drug Administration requires the completion of Phase III studies before the drug can be approved for sale in the U.S.
A Miracle in the Sea
"To me the sea is a continual miracle," Walt Whitman wrote. One of the miracles of the sea squirt is its fundamental resemblance to humans in several ways, including an immune system. British scientists have used sea squirts in human fertility research for a number of years.
"The sea squirt evolved about 550 million years ago, long before humans appeared and they are the closest relatives of vertebrates," added Dagit. "It's amazing that the sea squirt and humans are similar in some important ways. The squirt has many similar genes as humans, and they happen to be genes that can cause disease when they malfunction. When genes malfunction in humans, diseases such as cancer occur."
Scientists believe that the sea squirt was the first creature to develop an immune system. Researchers hope to understand how the human immune system is organized by drawing parallels to the more simple immune system in the sea squirt. For example, sea squirts, like humans, will reject foreign tissues introduced to their bodies.
Fox Chase Cancer Center, one of the nation's first comprehensive cancer centers designated by the National Cancer Institute in 1974, conducts basic and clinical research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu.
Fox Chase Cancer Center, part of Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase also was among the first institutions to receive the National Cancer Institute’s prestigious comprehensive cancer center designation in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are routinely recognized in national rankings, and the Center’s nursing program has achieved Magnet status for excellence three consecutive times. Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research and oversees programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE (1-888-369-2427).