Just-released research about a new class of drugs called “PARP inhibitors” is the most exciting development in cancer research in a decade or more. In just a few years it could save thousands of lives.
In the longer term, the drugs could represent a transformational approach to understanding and treating several forms of the disease.
All this enthusiasm is based on a small report published in the New England Journal of Medicine. It focuses on one clinical trial in its earliest stage in 60 patients with breast, ovarian and prostate cancer. Some — but not all — of the patients whose cancers seemed hopeless saw them shrink drastically or disappear. Many avoided the typical side effects — nausea, hair loss — associated with cancer treatment.
Of course, as with any good science, it is not just that one report that generates such excitement. The new research builds on many years of solid basic science and on other clinical trials that are either completed or in progress, which appear to show similarly dramatic reduction of certain breast, ovarian and prostate cancers.
The story of PARP inhibitors began in the early 1990s, when some scientists realized that breast cancer ran in certain families, and that some of the women in those families had an extraordinarily high — as much as a 90 percent lifetime risk — of getting the disease. There was a frantic and well-publicized hunt for the “breast cancer gene.” The hope was that finding the gene could provide crucial information about the cause of breast cancer and how to treat it.
BRCA1, BRCA2 raise risk for breast cancer
In September 1994, scientists from a company called Myriad Genetics and government researchers simultaneously won the race. It turned out there were two genes called BRCA1 and BRCA2. As they studied the genes, the researchers learned that they account for between 5 and 10 percent of all breast cancers, as well as a similar percentage of ovarian cancers and prostate cancers in men who are born with the mutated gene.
The immediate result of the gene discovery was that families and individuals at high risk could find out when they were affected. That continues to this day. But for those at risk, the treatment options are limited: surgical removal or close monitoring of the organs that might become cancerous.
What initially eluded the scientists was how BRCA1 and BRCA2 caused cancer. “We found the breast cancer gene, but we don’t know how it causes breast cancer,” one scientist famously quipped.
Years of hard work eventually revealed the mechanism. BRCA1 and BRCA2 produce proteins that repair mistakes in DNA that occur continually as cells in the body multiply normally. If a person is born with one defective of copy of one of the genes, the cells continue to grow but there is a far greater chance that an error will occur in the DNA that will cause cancer to arise.
PARP inhibitors kill cancer cells
The next big discovery came in 2005 when scientists found in lab experiments that they could make a drug, called a PARP inhibitor, that would interfere with the normal copy of the protein made from BRCA1 and BRCA2 genes. If cells have defective genes, when the drug is added, the DNA cannot be repaired at all. As a result, the cells die. And that is how PARP inhibitors kill cancer cells.
In experiments so far, the drugs have worked only in people with BRCA 1 and BRCA2 mutations resulting in breast, ovarian and prostate cancers. But there is evidence they may work in people without the mutations — particularly in cases of ovarian cancer for which better treatments are desperately needed.
The story of the PARP inhibitors is fine example of how research can move from the laboratory bench to the bedside, and it also shows how long and difficult journey can be.