cancer. They discovered that normal-looking cells in a tumor’s
microenvironment mutated in a way that enabled cells to multiply out of control. If those changes can be blocked, it would be
possible to stop cancer in its tracks.
“Several mutations are essential in driving cancer,” says Darrell
R. Borger, co-director of the translational research lab at Massachusetts General Hospital. “Those mutations might be very different
from one person to another, even in the same type of cancer. We’re
trying to get drugs that can effectively target those mutations.”
Identifying 200 cancer genes
One of the first mutations targeted was an overabundance of
receptors for the hormone estrogen in the cells of some breast
cancers. When estrogen binds to estrogen receptors (ERs) in the
cell, the hormone-receptor complex triggers the expression of
genes that promote cell growth.
That discovery led to the drug tamoxifen. Unlike earlier cancer-
treating drugs, it was created for a specific set of patients, those
over-expressing ERs. Tamoxifen inhibits the growth of breast
tumors by blocking the ERs, thereby reducing the amount of
tumor-promoting estrogen in the cells.
Outsmarting Cancer: Researchers
work to overcome drug resistance
Nearly all new discoveries are centering on cancer genetics. While it may seem that science has finally found cancer’s
Achilles’ heel, the view from the trenches isn’t quite so rosy.
For example, the widely heralded, targeted lung cancer drug
erlotinib extends patients’ lives by only several months, while
Herceptin cures breast cancer in just over half of HER2-positive
patients— and that’s assuming it’s given early in the disease.
The reason that even the most promising treatments fail to
cure many patients lies in cancer’s incredible complexity. For
every discovery of a potential cure comes a discovery of how
cancer can evade that cure. “The cancer genome is very unsta-
ble,” explains Cynthia Ma, director of developmental therapeu-
tics in breast oncology at Washington University in St. Louis,
“and cancer cells can develop resistance to targeted therapy.”
Many scientists are trying to find out why. A team from
Memphis and Ontario may have found a piece of that puzzle in
a study they published early this year in the journal Nature. They
discovered that cells taken from leukemia patients don’t have
just one cancer-causing mutation. Rather, they have distinct
families of cells with different types of mutations. That could
explain why even cancers treated with targeted drugs relapse.
The dominant family, which shows up in genetic profiling, may
succumb to treatment, only to be supplanted by a different fam-
ily with a resistant mutation.
When cancer that’s been treated spreads, biopsies may be
tough to obtain. Some researchers hope to overcome that road-
block with a blood test for mutations. “We’re looking for less
invasive techniques,” notes Darrell R. Borger of Massachusetts
General Hospital. “One way is to look for circulating tumor cells
in the blood.” His lab is experimenting with a blood test in a
partnership with Johnson & Johnson, which is developing tech-
nology to count and genetically profile cancer cells circulating in
the blood. These “escapees” can spread cancer to other organs.