Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance

By M. Thakur, Fernando Salangsang, Allison S. Landman, William R. Sellers, N. Pryer, M. Levesque, R. Dummer, M. McMahon, D. Stuart. Nature, 2013

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Patient Derived Xenograft Models: An Emerging Platform for Translational Cancer Research (2014, background): “Not only was a mechanism of resistance was identified, but also a novel drug administration strategy applicable to the clinic was proposed to overcome resistance (45).”
Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future. (2017, positive): “Stuart and colleagues demonstrated how vemurafenib resistant melanomas can exhibit drug dependency, such that an intermittent rather than continuous dosing of the drug can forestall the onset of lethal drug resistance (Das Thakur et al., 2013).”
Predicting evolution (2017, background): “For example, a xenograft mouse model of melanoma shows increased survival when the drug is withdrawn at predefined time points 132 , and fitness modelling of these dynamics predicts how the drug protocol can be optimized based on real-time measurements to further increase survival 134 .”
Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies (2023, background): “422 In pursuit of curation approach for melanoma patients with BRAF mutations, researchers have proposed that modifying dosing patterns could prevent the development of lethal drug resistance and extend the durability of BRAFi responses.”