Recent research has discovered in the lab a way to overcome drug resistance in colorectal cancer. This recent article explains the the findings and it is great news!
The results, which highlight the use of a novel drug called
ARI-4175, may eventually point to new approaches that can be used in
treating other cancers
When combined with other treatments, the drug cetuximab—which
works by slowing or stopping the growth of cancer cells—has been shown
to extend survival in certain types of cancer, including metastatic
colorectal cancers. Unfortunately, about 40 percent of colorectal cancer
patients—specifically those who carry a mutated form of a gene called
KRAS—do not respond to the drug. Researchers at Fox Chase Cancer Center
in Philadelphia, however, have been working on a way to overcome this
resistance to cetuximab by unleashing a second cetuximab driven
mechanism using a novel drug called ARI-4175.
In mice that had KRAS mutated colorectal cancer, researchers
found that ARI-4175 not only blocked tumor growth when used alone, but
also when used in combination with cetuximab. They hypothesize that the
new drug may work by enlisting "natural killer" cells of the body's own
immune system to reject the tumor.
"We've discovered that ARI-4175 appears to increase the level of
natural killer cells that could play a role in rejecting the tumor,"
Hossein Borghaei, DO, director of thoracic medical oncology at Fox Chase
and lead author on the study says. He notes that this action—rallying
the body's own immunologic defenses—may explain why ARI-4175 effectively
stops the growth of tumors. "My theory is that this particular drug
turns on the host's anticancer immune response, while cetuximab serves
to help direct it toward the cancer."
Borghaei, along William W. Bachovchin, PhD, professor of
biochemistry at Tufts Sackler School of Graduate Biomedical Sciences
(also co-author on the study) and colleagues, tested ARI-4175 in
colorectal cancer cell lines and in mice with two types of
cetuximab-resistant colorectal tumors.
Neither cetuximab nor ARI-4175, separately or together, succeeded
in killing the cells in lab dishes. In the mice, however, ARI-4175
blocked tumor growth, and was more successful at higher doses of the
drug. The research shows an even stronger effect in mice that received
ARI-4175 combined with cetuximab.
Cetuximab, which is FDA-approved for metastatic colorectal cancer
and some head and neck cancers, works by blocking a crucial receptor on
the surface of a cancer cell—causing the cell to die. In people
carrying the mutated form of the KRAS gene, cetuximab is not effective,
but ARI-4175 may open up a detour around that impasse.
Borghaei notes that a cancer treatment like the immune stimulator
ARI-4175, which uses the body's own defenses, may be more effective
than drugs targeting tumor oncogenes that are susceptible to mutations
that lead to resistance. "Tumors often develop resistance to targeted
therapies," he says, "but it's more difficult to find resistance to a
patient's own immune system. Bringing in the activity of the immune
system might be the most effective way to fight some of these cancers."
"Our immune system can actually be a very useful partner in the fight against cancer," he says.
The researchers say their results suggest ARI-4175 warrants
further testing in clinical trials. Although the researchers
investigated colorectal cancer, their findings may also point to new
approaches to treating other types of cancer. "If we can show that the
drug overcomes resistance to cetuximab, it can be used against head and
neck cancers as well," says Borghaei.