Innovation in cancer discovery moves in a cycle, rotating from the bedside to the laboratory and back again until the problem is solved. Laboratory discoveries help us understand the cellular events that lead to the formation and advancement of tumor cells so that we can derive clinical applications that save patients. From smart vaccines to new classes of drugs, we have learned how to switch on a dormant immune system to fight cancer and how to use drugs to turn on silenced tumor suppressor genes or to block proteins contributing to cancer progression. When we can't cure the disease, we've used drugs that, in certain patients, keep tumor growth in check, holding the cancer in a chronic phase. Biomarkers, genetic red flags that reveal important information about the initiation and spread of specific cancers, are being used in early detection, treatment, and in monitoring patients for recurrence of cancer. This is an exciting time in the Kimmel Cancer Center, where the laboratory and clinic have merged to introduce promising new therapies for a variety of cancers.
The cervical cancer vaccine developed by Drs. Connie Trimble and Drew Pardoll is one example. Though in an early stage, this vaccine offers a new twist, because it is aimed at curing disease, not preventing it. The vaccine targets HPV-16, the virus that causes cervical cancer. Other vaccines also being tested in our clinics are a breast cancer vaccine used in combination with low doses of two chemotherapy drugs for patients with late-stage breast cancer. With this vaccine, the body's immune cells may be able to seek out and destroy breast cancer cells throughout the body.
Surgeons and medical oncologists are developing an immune-boosting vaccine that uses a bacterium called listeria to target colon cancer cells that have spread to the liver. Listeria pushes the immune system to send the appropriate cancer-fighting cells to the liver and enables the immune system to recognize antigens on the cancer cells. Mouse studies have been successful and clinical trials are under way.
New drugs that zero in on the Achilles' heel of the tumor cell are another area of great promise. The drug astrasentan is one of these. It has been shown to stabilize the spread of cancer in many men with advanced prostate cancer who have stopped responding to hormone therapy. The three-year international study of more than 1,000 men opens the door to potential new treatment options for this subset of patients. "Some of these men are looking for less toxic alternatives to chemotherapy at this point in their lives," says Dr. Michael Carducci. "By keeping the cancer from spreading to the bone, astrasentan can help prevent their pain and potentially postpone when they will need more aggressive treatment," he says. The FDA is reviewing the data in preparation for possible approval in 2005.
Drugs that re-activate tumor suppressor genes silenced by a cellular process known as methylation have been successfully used in certain leukemias, and other drugs, so-called inhibitor class compounds, are being used to block proteins that contribute to tumor formation and growth.
Perhaps more importantly, we've learned how to combine these drugs with other approaches, including radiation and vaccines, to tailor therapies to each patient's specific tumor characteristics.
Cornelia Trimble, M.D. and Drew M. Pardoll, M.D., Ph.D.
on Cancer
