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http://www.webmd.com/breast-cancer/news/20090624/experimental-pill-fights-inherited-cancer
Experimental Pill Fights Inherited Cancer
Study Shows PARP Inhibitors Curb Growth of Some Breast, Ovarian, Prostate
Tumors
By Charlene Laino
WebMD Health News
Reviewed by Louise Chang, MD
June 24, 2009 -- For the second time this month, researchers report
success using a novel type of anticancer pill to curb the growth of
inherited tumors that often defy standard treatment. Called olaparib, the
experimental pill is a member of a new class of drugs called PARP
inhibitors that prevent unstable cancer cells from repairing themselves.
Two-thirds of 19 patients with cancer caused by mutations in the BRCA1 or
BRCA2 genes responded to treatment with olaparib, and in more than half,
tumors shrank or stopped growing, says researcher Johann de Bono, MD, PhD,
of the Institute of Cancer Research in Sutton, U.K.
Defects in the BRCA1 and BRCA2 genes place women at sharply increased risk
of developing aggressive cancers of the breast and ovaries at a young age.
BRCA2 gene mutations also raise a man's risk of prostate cancer.
Of 19 patients in the study with BRCA-inherited cancers, 15 had ovarian
cancer, three had breast cancer, and one had prostate cancer.
Olaparib did not help 41 other patients with tumors that were not
associated with BRCA mutations, de Bono says.
PARP inhibitors "will very likely change the way we treat patients" whose
tumors are caused by BRCA defects, says Daniel Silver, MD, PhD, of the
Dana-Farber Cancer Institute in Boston. Silver, who was not involved with
the work, co-authored an editorial about the study.
The study appears in the June 25 issue of The New England Journal of
Medicine.
PARP Inhibitors for Cancer: How They Work
PARP is short for poly (ADP-ribose) polymerase, an enzyme used by cancer
cells to repair DNA damage.
All cells, cancerous and healthy alike, have multiple systems for DNA
repair. Even if one pathway is turned off, most cells can survive.
In people with BRCA mutations, one pathway is shut down, much like a table
that is missing one leg. The table can still stand on three legs, but it's
unstable.
Along comes olaparib, knocking out the PARP pathway. Like a table that
only has two legs left, the cancer cell falls over and dies, de Bono says.
Like other targeted therapies -- smart drugs that take aim at the nuts and
bolts of tumor growth while leaving healthy tissue relatively unscathed --
PARP inhibitors cause fewer side effects than traditional chemotherapy, he
tells WebMD.
The most common side effects in the study were low-grade fatigue and mild
stomach upset.
"My prostate cancer patient, who had advanced cancer that had spread to
the bone, has been taking olaparib for two-and-one-half years. The drug is
really active, and the only side effect is indigestion," de Bono says.
Another advantage of olaparib is that it's a pill that only has to be
swallowed twice a day, he says.
PARP Inhibitors Targets Other Cancers, Too
PARP inhibitors will likely prove beneficial for other cancers, too,
Silver tells WebMD.
In fact, they are already being tested in women with so-called
triple-negative breast cancer. Such tumors are hard to treat because they
lack receptors for the hormones estrogen and progesterone as well as the
protein HER2, which are targeted by current therapies.
The hope is that eventually PARP inhibitors could be used at an early
stage to treat or even prevent cancer in high-risk persons, Silver says.
Maker AstraZeneca, which helped to fund the work, plans to continue
studying the drug, according to James Carmichael, MD, global medical
director for olaparib. |
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