RBx10080307, a dual EGFR/IGF-1R inhibitor for anticancer therapy.

Pharmacological intervention of epidermal growth factor receptor (EGFR) family members by antibodies or small molecule inhibitors has been one of the most successful approaches for anticancer therapy. However this therapy has its own limitations due to the development of resistance, over a period of time. One of the possible causes of the development of resistance to the therapy with EGFR inhibitors could be the simultaneous activation of parallel pathways. Both EGFR and insulin like growth factor-1 receptor (IGF-1R) pathways are reported to act reciprocal to each other and converge into the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. Inhibiting one pathway alone may therefore not be sufficient and could be a cause of development of resistance. The other cause could be mutations of EGFR which would be less sensitive to the inhibitors. We, therefore, suggest that co-targeting IGF-1R and EGFR kinases by dual inhibitors can lead to improved efficacy and address the problems of resistance.