Nearly all cancer patients eventually develop a resistance to chemotherapy that complicates treatment and increases the risk of death. But scientists have discovered a key factor that drives drug resistance – information that could help improve the effectiveness of therapy and buy time for patients with advanced cancer.
A team of scientists led by Fred Hutchinson Cancer Research Center say they have found that a type of normal, noncancerous cell in the body – called a fibroblast – sustains DNA damage when exposed to chemotherapy that ultimately drives the production of growth factors that stimulate cancer growth. Under normal circumstances, fibroblasts help maintain connective tissue, and they play a critical role in wound healing and collagen production.
But chemotherapy changes the game and turns fibroblasts into cancer promoters in patients with solid tumors, such as those with breast, prostate, lung and colon cancer that has spread throughout the body.
"Cancer cells inside the body live in a very complex environment or neighborhood,” said Dr. Peter S. Nelson, who reported on the team’s findings in the journal Nature Medicine. “Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy."
Specifically, the researchers found that chemo coaxes fibroblasts to crank out high levels of a protein that enables cancer cells to grow, invade surrounding tissue and resist chemotherapy. The discovery suggests finding a way to block this process may improve the effectiveness of therapy.
"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,” said Nelson. “Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies."
The National Institutes of Health, the National Cancer Institute, the Department of Defense and the Prostate Cancer Foundation funded the research.