There's a buzz among doctors and researchers about new inhibitor drugs that target a tumor's resistance to primary cancer treatments
The next breakthrough cancer drug could be a pill that induces cancer cells to destroy themselves. Or it may be a drug that turns off the cancer cell's ability to multiply and spread. It may even be a vaccine that convinces the body's own immune system to attack tumors. These were among the dozens of novel developmental-stage drugs with early clinical results showcased this week at the world's premier cancer meeting.
Although most of the headlines at the annual American Society of Clinical Oncology (ASCO) conference in Chicago June 1-5 focused on new uses for cancer drugs already on the market, many scientists at the meeting say they are most interested in drugs that may not be ready for the center stage until 2008 or 2009. "We are not going to have big breakthroughs every year, and this is a quieter meeting," says George Demetri, a top researcher at Dana-Farber Cancer Center in Boston. "But I'm already looking forward to next year."
Demetri and other scientists are particularly intrigued by a new class of drugs that target a cell defense mechanism called heat shock protein 90, usually referred to as HSP-90. The mechanism springs to action when a cell is exposed to heat and other stresses such as a toxic anticancer drug. In tumors, HSP-90 keeps the cells from dying off. Disable it, and the cells essentially commit suicide.
Advanced Trials Up Next
As Demetri describes it, HSP-90 looks something like a lobster claw that wraps itself around those parts of a malignant cell that help it to spread and grow—a sort of chaperone or bodyguard that allows the cancer to survive attacks. Armed thusly, cancer cells can develop resistance to drugs, so a number of companies have developed HSP-90 inhibitors to help the primary treatment do its job. These inhibitors, designed to work on a broad range of cancers, help ensure that tumors do not learn to resist the primary treatment.
Kosan Biosciences of Hayward, Calif., has based most of its research on HSP-90 inhibitors, designing them to work in combination with a number of primary treatments. At ASCO, the company presented data on several ongoing studies of its two main drugs, Tanespimycin and Alvespimycin (cancer drug names tend to be as complex as their mechanism of action). Tanespimycin is being tested against the blood cancer multiple myeloma, in combination with Velcade, a primary treatment made by Millennium Pharmaceuticals (MLNM).
Kosan Chief Executive Officer Dr. Robert Johnson says the interim results from an early-stage clinical trial with 56 patients found enough antitumor activity to warrant moving the drug into advanced trials this summer, with a goal of applying for Food & Drug Administration approval in the next year or so. "It could be the first HSP-90 inhibitor to reach the market," he says.
Optimism and Interest
It is not the first HSP-90 inhibitor to be developed, however. The National Cancer Institute has spent more than a dozen years testing a similar drug, called 17-AAG, but with little progress, because the inhibitor was not easily absorbed into the blood. Infinity Pharmaceuticals of Cambridge, Mass., has come up with a water-soluble version of 17-AAG called IPI-504 that it is developing in partnership with MedImmune (MEDI). IPI-504 is designed to overcome resistance to Novartis' Gleevec, the most effective treatment for a stomach cancer called GIST.
Data presented at ASCO from an early-stage trial of IPI-504 involving 21 GIST patients showed that it was able to decrease tumor activity or cause the disease to stabilize in a majority of patients, with minimal side effects. "We're really pleased with this drug so far," says Demetri, a principle investigator of the drug. "It certainly warrants further study."
Whether any of these drugs, or the hundreds of others presented at the meeting, will reach the market is far from certain—some 90% of experimental treatments fail in clinical trials. Still, says Larry Norton of Memorial Sloan-Kettering Cancer Center in New York, "I think next year's meeting will be very interesting."