Abstract
This chapter exploits translational aspects of epistructural physics to develop a multi-target molecular therapy against cancer metastasis. The goal is to optimize a therapeutic agent capable to realizing a dual blockade of the signaling pathway that uses the focal adhesion kinase (FAK) as signal transducer to prevent the onset of the invasive phenotype. Thus, the epistructure-based optimization of lead compound TAE226 (Pfizer) enables a careful control of the multi-target impact towards kinases of therapeutic interest to block cancer progression, including FAK, JNK and the IGF1R kinase. The molecular therapy requires synergy with a second drug that is optimized to block the recruitment of the PI3K/mTOR pathway conferring drug resistance. The uniqueness of the drug combination arises from the reciprocal editing (cf. Chap. 12), whereby the first drug abrogates resistance to the second drug which is itself an inhibitor of drug resistance towards the first drug.
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Fernández, A. (2016). Epistructural Drug Design to Treat Cancer Metastasis and the Associated Drug Resistance. In: Physics at the Biomolecular Interface. Soft and Biological Matter. Springer, Cham. https://doi.org/10.1007/978-3-319-30852-4_17
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DOI: https://doi.org/10.1007/978-3-319-30852-4_17
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