May 25, 2001

ASCO: View of cancer changing

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Dr. Carlos Arteaga was a guest speaker at the ASCO conference.

ASCO: View of cancer changing

Cancer specialists predicted the start of a “sea change” in how they think about cancer during the recent annual meeting of the American Society of Clinical Oncology in San Francisco.

The ability to target specific enzymes that make cancer cells different from normal cells is becoming a closer reality, illustrated by the recently approved “leukemia pill” Gleevec. As a result, oncologists attending the meeting said that classification of tumors in the future may be based more on the molecular events contributing to the cancer, rather than body site where the cancer occurs.

“The theme of this meeting is molecular targeting – everyone is talking about it,” said Dr. Mace Rothenberg, Ingram Professor of Cancer Research and director of Vanderbilt-Ingram Phase I Drug Development Program. “This may make us rethink cancer. For example, we may begin to classify cancers as ‘EGF receptor-positive tumors’ rather than ‘a breast tumor’ or ‘a lung tumor,’ and then treat accordingly.”

ASCO is the largest international organization of physicians who treat cancer. More than 25,000 people attended the annual meeting here, including a large group of Vanderbilt-Ingram physicians. Vanderbilt-Ingram physicians were co-authors on more than 30 abstracts presented at the meeting, ranging in topics from new targeted agents to new combinations of chemotherapy to easing treatment side effects.

Gleevec, approved by the FDA just two days before ASCO’s opening session, inactivates at least three enzymes called tyrosine kinases, including one that causes chronic myeloid leukemia. Tyrosine kinases play a key role in communicating growth signals to the nucleus of cells.

One of the plenary papers at ASCO, presented by former Vanderbilt-Ingram researcher Dr. Charles Blanke, outlined early success in treating gastrointestinal stromal tumors (GISTs) with Gleevec. The drug also inactivates a tyrosine kinase, c-kit, implicated in as many as 80 percent of GISTs, which are notoriously difficult to treat. Dr. Jordan Berlin, assistant professor of Medicine and director of Vanderbilt-Ingram’s gastrointestinal cancer program, is helping to further evaluate the drug in patients with GISTs to better ascertain optimal dosing and implications for survival.

Still, speakers at the meeting cautioned that Gleevec and other targeting drugs will not provide a “magic bullet.” Gleevec is very specific against enzymes involved in a limited number of cancers, and CML, for which it has been approved, is caused by one single genetic abnormality. Other cancers, especially solid tumors, are likely to be caused by a combination of mutations.

An attractive target, however, is the epidermal growth factor receptor, which is expressed by an estimated third of cancers. Dr. Carlos Arteaga, Ingram Professor of Cancer Research, led an ASCO symposium that examined approaches to target the EGF receptor.

Early laboratory studies of EGF receptor targeting have shown “dramatic” anti-tumor effects, Arteaga said. However, he cautioned that “the cancer cell is way too smart and is endowed with an abundance of signaling pathways,” so blocking a combination of strategies will probably be needed.

For example, Dr. Stacy Moulder, an oncology fellow at Vanderbilt-Ingram, presented results of a study in breast cancer cell cultures that showed greater effects by combining an inhibitor of the EGF receptor with an antibody that blocks growth signals at a different point. The National Cancer Institute is currently reviewing a proposal to test the combination of Iressa, tyrosine kinase inhibitor, with the antibody Herceptin in patients with subtype of metastatic breast cancer.

Iressa is also being tested in a large national trial, led by Dr. David Johnson, Vanderbilt-Ingram’s deputy director, in patients with non-small cell lung cancer.