Breakthrough research finds key reason behind chemotherapy resistance in cancer patients

Developing resistance to chemotherapy is a nearly universal, ultimately lethal consequence for cancer patients with solid tumors—such as those of the breast, prostate, lung and colon—that have metastasized, or spread, throughout the body.

A team of scientists led by the Hutchinson Center has discovered a key factor that drives this drug resistance—information that ultimately may be used to improve the effectiveness of therapy and buy precious time for patients with advanced cancer.

“Cancer cells inside the body live in a very complex environment or neighborhood. Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy,” said senior author Dr. Peter Nelson, a member of the Hutchinson Center’s Human Biology Division.

Dr. Peter Nelson

Nelson and colleagues found that a type of normal, noncancerous cell that lives in cancer’s neighborhood—the fibroblast—when exposed to chemotherapy sustains DNA damage that drives the production of a broad spectrum of growth factors that stimulate cancer growth. Under normal circumstances, fibroblasts help maintain the structural integrity of connective tissue, and they play a critical role in wound healing and collagen production.

However, the researchers found that DNA-damaging cancer treatment coaxes fibroblasts to crank out a protein called WNT16B within the tumor neighborhood, or microenvironment, and that high levels of this protein enable cancer cells to grow, invade surrounding tissue and resist chemotherapy.

This discovery suggests that finding a way to block this treatment response in the tumor microenvironment 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,” Nelson said. “Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies.”