Patients with advanced colorectal cancer (CRC) still depend on chemotherapy regimens\nthat are associated with significant limitations, including resistance and toxicity. The contribution\nof tyrosine kinase inhibitors (TKIs) to the prolongation of survival in these patients is limited,\nhampering clinical implementation. It is suggested that an optimal combination of appropriate TKIs\ncan outperform treatment strategies that contain chemotherapy. We have previously identified a\nstrongly synergistic drug combination (SDC), consisting of axitinib, erlotinib, and dasatinib that\nis active in renal cell carcinoma cells. In this study, we investigated the activity of this SDC in\ndifferent CRC cell lines (SW620, HT29, and DLD-1) in more detail. SDC treatment significantly\nand synergistically decreased cell metabolic activity and induced apoptosis. The translation of the\nin-vitro-based results to in vivo conditions revealed significant CRC tumor growth inhibition, as\nevaluated in the chicken chorioallantoic membrane (CAM) model. Phosphoproteomics analysis of\nthe tested cell lines revealed expression profiles that explained the observed activity. In conclusion,\nwe demonstrate promising activity of an optimized mixture of axitinib, erlotinib, and dasatinib in\nCRC cells, and suggest further translational development of this drug mixture.
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