Some chemotherapy drugs shrink tumors at
first, but their action can also spur the bone marrow to produce cells called
CEPs, which rush to the site of the cancer to help rebuild the tumor's blood
supply, according to the study published in the September issue of the journal
But in their experiments with mice and
human cancer cells, Dr. Yuval Shaked of the Rappaport Faculty of Medicine at
the Technion-Israel Institute of Technology and an international team of
researchers discovered that not all chemo drugs have this effect on CEPs.
For instance, paclitaxel, a drug most often
used to treat lung, ovarian and breast cancer, appears to mobilize CEPs and
promote new blood vessel growth in treated tumors. But gemcitabine, a chemo
drug used to treat non-small cell lung cancer, pancreatic cancer, breast
cancer, and bladder cancer, does not trigger increased CEP activity, the
The difference could explain why a
combination of chemotherapy and antiangiogenic drugs—drugs that block new blood
vessel formation—prevent the regrowth of some tumors but fail to have any
effect on other tumors, explained senior author Robert S. Kerbel of the
University of Toronto.
Antiangiogenic drugs appear to be most
effective when they team up with chemotherapies that unleash CEPs, the
researchers suggest, since they can blunt the effects on new blood vessel
growth prompted by the cells.
In fact, the results indicate that an
antiangiogenic drug given "immediately prior" to a chemotherapy drug that
causes a spike in CEPs can shrink tumors and kill off tumor cells, said Shaked,
who completed the study at Sunnybrook Health Sciences Centre in Toronto,
But "little or no enhanced antitumor
activity is obtained when it is combined with a chemotherapy drug that does not
induce such a CEP spike," the researchers note in the study.
The researchers also identified key
elements of the molecular pathway that links certain chemo drugs to the
mobilization of CEPs. By targeting one part of the pathway with particular
antibodies in mice, "we can blunt the chemotherapy-induced CEP spike," Shaked
said. If a similar antibody could be developed for clinical use in humans, it
might improve the antitumor capabilities of some chemotherapies, he explained.
Dr. Shanin Rafii, a professor of genetic
medicine at Weill Medical College of Cornell University in New York City and
one of the pioneers of CEP research, said the Cancer Cell study is a "huge
advance" that will give clinicians a much needed way to detect how tumors
respond to certain chemotherapies.
Rafii said that the research may someday
lead to a simple blood draw for cancer patients, "a test that you can do
noninvasively, to judge how well a chemotherapy agent is targeting
angiogenesis" in a tumor. With that information in mind, clinicians could
combine antitumor drugs "in a much more logical manner," he noted.