The aging microenviroment promotes metastasis and therapy resistance


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Ashani T Weeraratna1
1Melanoma Research Center, The Wistar Institute, Philadelphia, USA

Abstract

The incidence of the vast majority of cancers is higher in populations over the age of 50. The effects of an aged microenvironment on tumour progression, prognosis and clinical outcome have been largely unexplored, and no age-based biomarkers or protein signatures for monitoring therapeutic response have been defined. Here, we perform a molecular analysis of how normally aging cells can affect tumour progression, using melanoma as a model. Individuals over the age of 50 have a much poorer prognosis for melanomas of equal grade and stage, compared to younger individuals. To date, the molecular underpinnings of this disparity have not been identified. Using transgenic mouse models of melanoma, as well the generation of artificial skin with human tumour cells and fibroblasts, we explored how the changes in aging affect tumour progression. Our results show that changes in the aging microenvironment drive metastasis and therapy resistance via mechanisms that involve Wnt signaling and response to ROS. These data suggest that the prognosis and treatment of cancer in aging individuals cannot be guided by recent advances and guidelines. Instead, new efforts must be made to understand and treat cancers in an age-appropriate manner.