The Breast Cancer Research Foundation
Donate Now WINTER 2010

Starve a Cancer, Feed a Cure



Angiogenesis: the very word is daunting. But break it down and it becomes a fundamental concept for understanding how tumors grow so well-stronger and faster even than the body's normal cells. "Angio," which stands for blood vessel, and "genesis," meaning new, or beginning, combine to explain a process that occurs in health and in a lot of diseases, including breast cancer.

Our bodies need new blood vessels—whenever there's an injury, even if it's a minor cut or bruise, and as we grow. This is angiogenesis, the formation of new capillaries, veins and arteries, and the process itself is not harmful. Tumors need blood vessels, too. Otherwise they don't grow. In typical violation of the body, cancers know a way to hijack angiogenesis and redirect it for an unsavory outcome. Individual tumor cells do this by releasing chemicals that recruit the body's construction crew to do their bidding.

It all started with
Judah Folkman, MD, the renowned Harvard scientist who in 1993 revealed and proved to the world's research community how this biological process works, and who was honored with BCRF's Jill Rose Award in 1997 for his related research, presented the latest news on angiogenesis at the annual scientific retreat (which is underwritten each year by Muriel Siebert) and public symposium in New York on October 15 and 16. According to Folkman, the good news is that the field of anti-angiogenesis cancer therapy is "beginning to be reminiscent of HIV or tuberculosis." By this he meant that multiple new drugs for inhibiting angiogenesis have reached the market with FDA approval. Since numerous organic molecules are part of angiogenesis, and each drug prevents just one from doing its dastardly job, cancer doctors are now beginning to test the growing arsenal in various combinations to fight breast cancer. Like the evolution of treatments for HIV and TB, treatments for cancer may be more potent when used together rather than as single agents.

One of the pitfalls of treating cancer angiogenesis, as scientists have learned following Folkman's pivotal discoveries, is that blocking one tumor angiogenesis promoter will halt the cancer's growth only for a short while. Then the tumor will come raging back into blood-supply fueled growth because it learns how to evade the "single-channel" treatment. But in the body, what gets turned on must also get turned off. In normal angiogenesis there are "off" chemicals to halt the process of new blood vessel growth when it is no longer needed. Perhaps the most exciting news in the angiogenesis field is that in addition to synthetically engineered angiogenesis inhibitors in the form of drugs, Folkman and other scientists are studying ways to coax into action the body's own chemistry that would naturally put the brakes on the process. Though only Folkman's wife and a handful of colleagues initially supported his 1971 hypothesis that cancers rely on angiogenesis, the entire field of cancer research now embraces his theory.

Id Proteins
Robert Benezra, PhD, a research scientist at Memorial Sloan-Kettering Cancer Center in New York City, described a different approach toward curbing angiogenesis. He studies a group of proteins called "Ids." Two of them, Id1 and Id3, are produced in the body's well of primordial cells in the bone marrow, where many angiogenesis cells also originate. Benezra's plan is to block cells that aid in angiogenesis by inhibiting the Id proteins. If proven, this strategy would nip angiogenesis in the bud, and preempt tumor evasion of anti-angiogenic drugs. With BCRF support, Benezra's lab is currently in preclinical studies with two experimental agents that so far look promising in blocking Id proteins.

Promacs
Another BCRF researcher, Laura Esserman, MD, of the University of California at San Francisco, has sleuthed out an immune system cell that is found in the same cellular "neighborhood" where tumor angiogenesis occurs. These "promacs" or proliferating macrophages, are present when magnetic resonance imaging (MRI) shows fast-growing angiogenic tumors. Promacs are a welcome new marker for breast cancer screening, and if reliable, may help identify a specific tumor type that might benefit from new treatment strategies.

Since there are many varieties of macrophages in the body, Esserman and her colleagues (among them BCRF grantee Funmi Olopade) are conducting further tests to determine which macrophages are diagnostically relevant in breast cancer imaging. The research community's growing knowledge of angiogenesis and inflammation provides a new way of measuring and categorizing breast cancer, it turns out.

George Sledge, Jill Rose Awardee
When George Sledge, MD, of Indiana University School of Medicine, and BCRF Executive Board of Scientific Advisors member Nancy Davidson, MD, presented the latest news in clinical trials related to angiogenesis, Sledge had to let fellow BCRF grantees know that "with Judah Folkman here today, I feel like a theologian at the podium discussing the book of Genesis, but with God sitting in the front row."

Dr. Sledge, who received this year's Jill Rose Award for outstanding contributions to the field of breast cancer research, described a new, 5000-patient, international clinical trial that will test whether the cure rate of early stage breast cancer can be improved by combining conventional adjuvant therapy and the anti-angiogenic drug, Avastin. This large trial is based on the results of work led by BCRF grantee Kathy Miller. Davidson, who as the Breast Cancer Research Professor of Oncology of the Sidney Kimmel Cancer Center of Johns Hopkins University, coordinates the BCRF-funded Translational Breast Cancer Research Consortium, explained. "We've doubled progression-free survival time in advanced breast cancers using Avastin in combination with Taxol." Though there was not an improvement in the overall survival with the combined therapy over chemotherapy alone among women with Stage IV breast cancer enrolled in the study, Davidson said that the findings prove the principle that combining angiogenesis inhibitors with existing state-of-the-art drugs can alter the course of the disease. Giving those treatments earlier, as the new study is designed to do, may yield even more promising results.

Larry Norton, BCRF's Scientific Director, sagely noted that, "the person who takes the scientific discovery and implements it in people is often ignored in medical history." He was explaining at the October 16th BCRF public symposium preceding the Awards Luncheon that Sledge is a leader in implementing the use of angiogenesis inhibitors, both in the care of his patients and through coordination of clinical trials to systematically study the new class of cancer drugs. Honoring him with the eleventh annual Jill Rose Award underscores, as Norton put it, that "as an organization, BCRF will not overlook these important people."

At the awards ceremony, Sledge told the 1,100 attendees packing the Grand Ballroom at the Waldorf-Astoria, "I'm astonished to receive this award because my research is uniquely collaborative. If I deserve it, I deserve it on behalf of an army of researchers-nurses, statisticians and the women who participate in clinical studies." He added, "one could draw a direct line from laboratory research funded by BCRF to my work with patients. Evelyn Lauder, Larry Norton, Myra Biblowit—you're my heroes."