Some 90% of cancer patients with metastatic breast, prostate, lung or colon cancers develop resistance to chemotherapy, and now scientists may have a clue as to why.
In a recent study published in the journal Nature Medicine, researchers report that an excess of a protein called WNT16B, which is produced by fibroblast cells near tumors, may spur cancer cells to grow and invade surrounding tissue.
What goes awry? Under normal conditions, fibroblast cells, which are the main component of connective tissue like tendons, work to heal wounds and produce collagen to maintain cells’ structure. But when fibroblasts are doused with chemotherapy, it damages their DNA causing them to overproduce WNT16B — up to 30 times as much of the protein as they should, a finding that the study’s authors called “completely unexpected.”
While WNT16B has been previously implicated in the development of normal cells and in some cancers, it hasn’t been identified as a source of treatment resistance until now.
The researchers, from Fred Hutchinson Cancer Research Center, characterized the protein as an unfriendly “neighbor” that lives in the same environment as cancer cells. “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 in a statement.
Chemotherapy treatments are given in cycles in order to allow normal cells — and the patient — to recover from the toxic drugs. But the approach doesn’t always eradicate all tumors, allowing some to survive and evolve to become resistant to future rounds of treatment. “In the laboratory we can ‘cure’ most any cancer simply by giving very high doses of toxic therapies to cancer cells in a petri dish. However, in people, these high doses would not only kill the cancer cells but also normal cells and the host,” said Nelson.
The new research falls squarely in line with the idea that chemotherapy doesn’t just affect cancer cells, but also other cells, particularly those in and around tumors. “Sometimes this can be good — for instance, chemotherapy can stimulate surrounding healthy immune cells to attack tumors,” Fran Balkwill, a Cancer Research UK expert on the microenvironment of tumors, told BBC News. “But this work confirms that healthy cells surrounding the tumor can also help the tumor to become resistant to treatment.”
The researchers hope that by identifying the role of WNT16B, they can counter its effect and improve the effectiveness of chemotherapy.
“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 findings are published in the August 5 issue of Nature Medicine.