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Resistance to Targeted Therapies As a Result of Mutation(s) in the Target

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Targeted Therapies

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

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Abstract

Tyrosine kinase inhibitors (TKIs) are effective clinical therapies in a subset of malignancies defined by oncogenic alterations. Compelling clinical examples include EGFR mutant non-small cell lung cancer and chronic myeloid leukemia. Unfortunately, the effectiveness of these treatments is ultimately limited due to the development of drug resistance most commonly mediated by secondary mutations. These resistance mutations often occur at the gatekeeper residue, like the T315I mutation in BCR-ABL or the T790M mutation in EGFR, but it can also occur outside the gatekeeper residue. In this chapter, we will address the different types of resistance mutations and the mechanisms by which they confer resistance to TKI. We will also discuss the therapeutic strategies developed to overcome these resistance mutations.

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Authors and Affiliations

  1. Harvard Medical School, Lowe Center for Thoracic Oncology, Dana Faber Cancer Institute, Boston, MA, USA

    Pasi A. Jänne

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  1. Alexis B. Cortot
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  2. Pasi A. Jänne
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Correspondence to Pasi A. Jänne .

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  1. Health System, Deptartment of Microbiology and Cancer C, University of Virginia, Charlottesville, 22908-0734, Virgin Islands, USA

    Daniel Gioeli

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Cortot, A.B., Jänne, P.A. (2011). Resistance to Targeted Therapies As a Result of Mutation(s) in the Target. In: Gioeli, D. (eds) Targeted Therapies. Molecular and Translational Medicine. Humana Press. https://doi.org/10.1007/978-1-60761-478-4_1

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