P53 mutations in stromal fibroblasts sensitize tumors against chemotherapy

Int J Cancer. 2008 Aug 15;123(4):967-71. doi: 10.1002/ijc.23546.


The efficacy of chemotherapy is usually viewed as the outcome of cancer-cell-autonomous processes while the contribution of stroma is being overseen. Here we show that p53 mutations in stromal fibroblasts, a genetic lesion that is detectable in primary breast, prostate and probably other cancers, while they accelerate tumorigenesis they also sensitize tumours against conventional chemotherapy by doxorubicin and cis-platinum. The mechanism by which p53 of stromal fibroblasts affects the response of a tumour against chemotherapy is likely to involve the induction of senescence in the fibroblasts which in turns results in the production of growth factors acting onto the cancer cells by paracrine mechanisms. Our findings identify stromal fibroblasts as important modulators of the efficacy of anticancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Animals
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Doxorubicin / pharmacology
  • Female
  • Fibroblasts / pathology
  • Fibroblasts / physiology
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Mutation
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Stromal Cells / pathology
  • Stromal Cells / physiology
  • Tumor Suppressor Protein p53 / genetics*


  • Antineoplastic Agents
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Cisplatin