Juric and Castel et al. examined the development of resistance to the PI3K p110α inhibitor BYL719 in a patient with metastatic breast cancer who had responded initially, but later relapsed and died. The authors collected samples from 14 metastatic sites during rapid autopsy and found that all lesions had loss of one copy of PTEN, and those that had developed resistance to BYL719 treatment had heterogeneous genetic alterations that resulted in the complete loss of PTEN expression. This suggests that parallel evolution occurs at metastatic sites, leading to the same phenotypic outcome in all of them.
References
Juric, D. & Castel, P. et al. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor. Nature http://dx.doi.org/10.1038/nature13948 (2014)
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Seton-Rogers, S. Different means to the same end. Nat Rev Cancer 15, 2 (2015). https://doi.org/10.1038/nrc3886
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DOI: https://doi.org/10.1038/nrc3886
