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Using Systems Pharmacology to Advance Oncology Drug Development

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Systems Pharmacology and Pharmacodynamics

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 23))

Abstract

Cytotoxic chemotherapies have been the foundation of oncology for the last 50 years. The emergence of molecularly targeted anti-cancer drugs promises to deliver inherently safer and more effective treatments by attacking the unique biochemical vulnerabilities of tumor cells. However, the promise of these agents is fundamentally limited by the heterogeneity of cancer genomes and the robustness of protein signaling networks which control tumor cell growth. By quantifying these cellular and molecular properties, computational systems biology has the potential to accelerate progress and increase success rates of anti-cancer drug development programs. Mechanism-based computational models which integrate molecular cell biology and drug pharmacology may thus enhance the predictive power of pre-clinical research, the utility of clinical data, and ultimately inform critical drug development decisions. Examples are provided through which orthogonal computational modeling approaches , from data-driven statistical models to physicochemical-based differential equations, have been used to address challenges arising at different stages of such programs. These include drug target selection , therapeutic design , identification of biomarkers for patient stratification , dose selection , and the design of combination regimens.

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Acknowledgments

I would like to thank Brigit Schoeberl, Ulrik Nielsen, Matthew Onsum, Charlotte McDonagh, Johanna Lahdenranta, Jinyan Du, Yamsin Hashamboy-Ramsey, Bart Hendricks, Petra Loesch, and Debbie Tseng providing helpful feedback on the manuscript, and many other colleagues at Merrimack Pharmaceuticals who have contributed ideas and supported this work over the years.

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Kirouac, D.C. (2016). Using Systems Pharmacology to Advance Oncology Drug Development. In: Mager, D., Kimko, H. (eds) Systems Pharmacology and Pharmacodynamics. AAPS Advances in the Pharmaceutical Sciences Series, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-319-44534-2_19

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