Chemotherapy damages normal tissue, causing it to secrete novel factors that sustain the growth of residual tumor cells, leading to treatment resistance, reports a study published online this week in Nature Medicine.
Peter Nelson and colleagues studied the effects of a subtype of cancer chemotherapy regimes that cause DNA damage and trigger an inflammatory response on normal fibroblast cells found in the environment of prostate tumors. This reaction to chemotherapy in the normal tissue stimulates the secretion of the protein, Wnt16B, by fibroblasts, which is then taken up by neighboring tumor cells. Wnt16B acts to trigger oncogenic signaling pathways fostering survival of cancer cells and dampening the response to chemotherapy.
The study also reports that Wnt16B is elevated in the normal tissue surrounding tumors of human breast, ovarian and prostate cancer patients after chemotherapy treatment, supporting the importance of this tumor microenvironment signaling pathway in therapy responses.