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Clinical Development of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors: What Lessons Have We Learned?

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Targeted Therapies in Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 610))

The epidermal growth factor receptor (EGFR) was selected as a strategic target for anticancer drug development almost two decades ago. This was based on evidence of receptor over-expression in human cancer and association with worse prognosis. Therapeutic strategies were developed and showed preclinical evidence of antitumor effects in animal models of EGFR-driven tumors. The fundamental process leading to EGFR dysregulation in human cancer were not known at that time. These agents were among the first class of targeted agents to enter the clinic at a time when the need to change the clinical development process use for cytotoxic agents to accommodate this new class of drugs was starting to be discussed. Two areas were of major interest. One was to base dose selection in pharmacodynamic endpoints rather than toxicity-based criteria. The second was to elucidate which patients are more likely to respond to these agents. Over the last few years this has been an important area of research. We have learned that while pharmacodynamic endpoints are ideal, the lack of robust and well validated analytical methods may lead to the wrong dose selection.

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Authors
  1. Manuel Hidalgo M.D., Ph.D.
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  1. Nerviano Medical Sciences, 10 Viale Pasteur, Nerviano (Milano), 20014, Italy

    Francesco Colotta

  2. Istituto Clinico Humanitas and Institute of Pathology, University of Milan, 56 Via Manzoni, Rozzano, Milano, 20089, Italy

    Alberto Mantovani

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Hidalgo, M. (2008). Clinical Development of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors: What Lessons Have We Learned?. In: Colotta, F., Mantovani, A. (eds) Targeted Therapies in Cancer. Advances in Experimental Medicine and Biology, vol 610. Springer, New York, NY. https://doi.org/10.1007/978-0-387-73898-7_10

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