When chemotherapy fails for cancer patients with solid tumors, it is usually because the cancer has developed a resistance to chemotherapy. A new study may have found one of the mechanisms by which some cancers may continue to grow and spread despite repeated rounds of chemotherapy.
Researchers led by Fred Hutchinson Cancer Research Center discovered that the microenvironment surrounding a tumor can play a role in spurring cancer growth and resistance to chemotherapy.
Specifically, a normal, noncancerous cell called a fibroblast located near a tumor can sustain DNA damage when exposed to chemotherapy. This drives the production of a broad spectrum of growth factors that stimulate cancer growth.
Normally, in a healthy person, fibroblasts help maintain the structural integrity of connective tissue, and they play a critical role in wound healing and collagen production. But when chemotherapy damages the DNA of fibroblasts, they pump out a protein called WNT16B within the tumor microenvironment. High levels of this protein enable cancer cells to grow, invade surrounding tissue and resist chemotherapy.
The researchers detected up to a 30-fold increase in WNT production, a result that both stunned and surprised them. It was known that WNT genes and proteins play a role in normal development and the development of some cancers, but it was not known to play a significant role in treatment resistance.
"Cancer therapies are increasingly evolving to be very specific, targeting key molecular engines that drive the cancer rather than more generic vulnerabilities, such as damaging DNA. Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies." said senior author Peter S. Nelson, M.D., a member of the Hutchinson Center's Human Biology Division.
The researchers believe the next step will be to find a way to block this response to chemotherapy in the tumor environment, and hopefully eliminate this path of drug resistance.
Medical News Today
Fred Hutchinson Cancer Research Center