Serum IGF1 is a new prognostic marker for resistance to targeted therapies and a predictive marker for anti-IGF1R therapy in melanoma

In a prospective clinical study, we show that increased serum IGF1 levels in a patient may be a predictive marker of melanoma escape to therapies targeting MAPK pathway (BRAFi/MEKi). In addition, our in vitro and in vivo studies suggest that the response of targeted therapies-resistant melanoma cells to IGF1R inhibitor appears to correlate with the level of IGF1 secretion. Overall, our results suggest that monitoring serum IGF1 levels would individually identify melanoma patients who escape BRAFi/MEKi treatment and may benefit from a combination of targeted therapies and IGF1 signaling inhibition to overcome resistance. Overall design: To investigate the role of the IGF1 pathway in resistance to therapies targeting proteins BRAF and MEK in melanoma, we established human menlanoma cell lines resistant to BRAF and MEK inhibitors.