Mesenchymal stroma: primary determinant and therapeutic target for epithelial cancer.
Multifocal and recurrent epithelial tumors, originating from either dormant or de novo cancer cells, are major causes of morbidity and mortality. The age-dependent increase of cancer incidence has long been assumed to result from the sequential accumulation of cancer-driving or -facilitating mutations with induction of cellular senescence as a protective mechanism. However, recent evidence suggests that the initiation and development of epithelial cancer results from a close interplay with its altered tissue microenvironment, with chronic inflammation, stromal senescence, autophagy, and the activation of cancer-associated fibroblasts (CAFs) playing possible primary roles. We will discuss recent progress in these areas, and highlight how this understanding may be used for devising novel preventive and therapeutic approaches to the epithelial cancer problem.
Cutaneous Biology Research Center, Massachusetts General Hospital, 13th Street Building 149, Charlestown, MA 02129, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA.
Sandro
S
Goruppi
G Paolo
GP
Dotto
D000818:Animals; D001343:Autophagy; D016922:Cellular Senescence; D006801:Humans; D008648:Mesoderm / Q000473:pathology*; D058990:Molecular Targeted Therapy; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology* / Q000628:therapy*; D017154:Stromal Cells / Q000473:pathology
SASP; autophagy; senescence; skin cancer; stromal microenvironment