Innate or acquired resistance to chemotherapy presents an important and 
predictable challenge in cancer therapy. Malignant tumors consist of both 
neoplastic and benign cells such as stromal fibroblasts, which can influence the 
tumor's response to cytotoxic therapy. In a recent article in Nature Medicine, 
Sun et al. show that increased expression of Wnt family member wingless-type 
MMTV integration site family member 16B (WNT16B) by the tumor microenvironment 
in response to cytotoxic damage and signals through the canonical Wnt pathway to 
promote tumor growth and chemotherapy resistance. Such findings outline a 
mechanism by which cytotoxic therapies given in cyclical doses can actually 
augment later treatment resistance and may open the door to new areas of 
research and to the development of new therapeutic targets that block the DNA 
damage response program.