March 7, 2012 at 5:02 PM ET
By Robert Bazell
Chief science and medical correspondent
A single case reported Wednesday in the New England Journal of Medicine could indicate a significant change of the course of cancer treatment -- perhaps saving or prolonging thousands of lives.
For more than a century, scientists have been attempting to harness the immune system to fight cancer -- trying to get the antibodies and cells that protect us from bacteria and viruses to kill diseased cells. Every once in a while, a tantalizing success occurred. But time and again the treatment could not be repeated.
The case begins with a drug called ipilimumab, approved in 2011 for advanced melanoma treatment. The drug turns the immune system into a cancer-killer, bringing some patients back from the brinkof death. Melanoma is one of the deadliest forms of skin cancer, striking 76,000 Americans and killing more than 9,000 every year. Because there are few treatments for advanced melanoma, the new drug was greeted with excitement by doctors and patients. But ipilimumab, sold under the brand named Yervoy by Bristol Myers Squibb, works in only 10 percent to 20 percent of patients.
Until now, no one knew why.
Valerie Esposito, a 42-year-old mother of three, was taking ipilimumab for advanced melanoma and it wasn’t working very well. The cancer was spreading through her body. One huge tumor, in fact, was pressing on her spine. To relieve the pressure, her doctors at Memorial Sloan Kettering Cancer Center in New York radiated the lump. Within weeks, other tumors throughout her body started shrinking dramatically.
This has occurred before in cancer immunology. But this time oncologist Dr. Jedd Wolchok and his team of melanoma specialists at Sloan Kettering think they have figured out, at the molecular level, exactly how that shot of radiation altered her immune system to allow the drug to kill far more cancer cells. It created pieces of tumors -- proteins called antigens -- that sparked specific changes in how antibodies and disease-fighting white cells recognized the cancer cells as foreign and thus destroyed them. Already the researchers are planning a nationwide clinical trial to determine if the findings can allow the drug to help many more patients with advanced melanoma.
They also believe the same approach could work for kidney, lung and other cancers.
Other recent cancer research, also in the NEJM, demonstrated less promising results.
For decades, scientists have known that cancer occurs because of mutations that occur in adult cells in the genes that regulate cell growth. The ideas behind the current buzz words of 'targeted therapy” and “personalized medicine” postulate that researchers will understand the mutations in tumors and develop drugs to target them and stop the cancers. Indeed, a handful of such drugs have proved successful often in a relatively small percentage of cancers of one type or another.
Determining the sequence of genes in cancers and finding mutations, so-called tumor markers, has gotten increasingly cheaper and easier. As a result, the British scientists were able to show that within an individual's tumors, different mutations occur in different places and at different times. The implication is that even if one mutation is stopped others will win out through natural selection and continue driving the tumor to grow. As Dr. Dan Longo of Harvard points out in an editorial in the Journal “the simple view of directing therapy on the basis of genetic tumor markers is probably too simple.”
The search for cancer treatments has been a long, difficult struggle involving the efforts to understand some of the most fundamental aspects of life itself. We can expect , as we have seen today, steps both forward and back.
Copyright 2013 Thomson Reuters.