Anti-angiogenesis is now the fourth modality for treating cancer, preceded by surgery, radiotherapy, and chemotherapy. Angiogenesis inhibitors are offering greatly reduced toxicity, with none of these agents suppressing bone marrow or causing hair loss.
“As the toxicity of anti-cancer therapy begins to go down, researchers are now beginning to ask how much earlier it would be possible to treat cancer,” said Folkman, director, vasculature biology, Children’s Hospital, Boston, and professor, pediatric surgery and cell biology, Harvard Medical School, Boston.
“You can’t treat cancer really early with toxic drugs and, if you can’t see the cancer, radiotherapy and surgery are not very useful. What if you could treat cancer really early before anatomical location? If biomarkers could be made to have greater specificity you could begin to treat cancer years before its occurring,” Folkman said.
Folkman first published his ideas on angiogenesis inhibitors in 1971, based on his discovery that cancer growth depends on the formation of capillary blood vessels. Several anti-angiogenesis inhibitor drugs are now on the market or awaiting approval.
Compugen’s own efforts to find biomarkers of cancer and cardiovascular disease have been underway for just under two years. “The thinking was to find biomarkers that are generally associated with disease and could, therefore, be used for screening and early detection,” says Alon Amit, PhD, VP, science and technology commercial operations, Compugen. “There is a lot more to be done in this field of early detection in the coming years, much earlier than was previously imagined.”
Researchers will find it challenging, Amit says, to demonstrate that such biomarkers are actually working because they will have to retest patients and wait quite a few years to see if their predictions are correct.
The discoveries Compugen has made to date have enabled a recent string of licensing agreements with Diagnostic Products Corp., Los Angeles, Ortho-Clinical Diagnostics, Rochester, N.Y., a Johnson & Johnson company, and Biosite, San Diego, who are working to validate those biomarkers in the clinic. “The future will entail the use of biomarkers beyond detecting the disease or even monitoring disease progression or classification,” says Amit.
“There is a lot of buzz today about using biomarkers as part of the drug development process, which generally goes under the name surrogate markers, which could replace the clinical endpoints of a trial that are often difficult to measure or take a lot of time to measure. Having such sets of markers could make clinical trials much cheaper, faster, and better in terms of their predictive value.”
He says that they have developed methods that will enable them to define a new tier of markers that will be useful, not just for disease screening, but for the development of drugs.
Compugen’s current biomarker candidates are often splice variants. One example is a variant of Her-2, a marker used to find breast cancer patients who can be treated with Herceptin. The variant is believed to be secreted into the blood stream, rather than isolated in the tissue, making it more easily detectable as a way to diagnose Her-2-positive breast cancer patients.
“We have examples of markers that are known to be valid today but can only be used by techniques that detect their presence on the surface of cells, such as fluorescent in situ hybridization and immunohistochemistry. The problem with these techniques, however, is that you have to access to the actual tissue. It’s a great advantage when you have access to a protein that behaves similarly to this marker except that it is secreted through the blood stream.”
“No one has ever talked about diagnosing a less than 1mm-sized-tumor, like Dr. Folkman is today, five or six years before they become cancerous. We think that those things will happen and we want to be there when it does.”
By Elizabeth Tolchin