Systems Modeling Identifies Divergent Receptor Tyrosine Kinase Reprogramming to MAPK Pathway Inhibition

Targeted cancer therapeutics have demonstrated more limited clinical efficacy than anticipated, due to both intrinsic and acquired drug resistance. Underlying mechanisms have been largely attributed to genetic changes, but a substantial proportion of resistance observations remain unexplained by genomic properties. Emerging evidence shows that receptor tyrosine kinase (RTK) reprogramming is a major alternative process causing targeted drug resistance, separate from genetic alterations. Hence, the contributions of mechanisms leading to this process need to be more rigorously assessed.

Allison M. Claas, Lyla Atta, Simon Gordonov, Aaron S. Meyer, and Douglas A. Lauffenburger
Cellular and Molecular Bioengineering
Volume: 11
Number: 6
Pages: 451–469
Date: December, 2018
DOI: 451–469
ICB Affiliated Authors: Douglas A Lauffenburger