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Colorectal Cancer Growth Retardation through Induction of Apoptosis, Using an Optimized Synergistic Cocktail of Axitinib, Erlotinib, and Dasatinib. | LitMetric

Colorectal Cancer Growth Retardation through Induction of Apoptosis, Using an Optimized Synergistic Cocktail of Axitinib, Erlotinib, and Dasatinib.

Cancers (Basel)

Molecular Pharmacology Group, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, Switzerland.

Published: November 2019

AI Article Synopsis

  • * A newly identified drug combination of axitinib, erlotinib, and dasatinib shows strong potential in treating CRC, outperforming conventional chemotherapy methods.
  • * In lab studies, this drug combination effectively reduced CRC cell activity and promoted cancer cell death, and it also demonstrated significant tumor growth inhibition in animal models, warranting further research.

Article Abstract

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

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966484PMC
http://dx.doi.org/10.3390/cancers11121878DOI Listing

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