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Therapeutic Kinase Inhibitors pp 135–169Cite as

Will Kinase Inhibitors Make it as Glioblastoma Drugs?

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 355))

Abstract

Kinase inhibitors have emerged as effective cancer therapeutics in a variety of human cancers. Glioblastoma (GBM), the most common malignant brain tumor in adults, represents a compelling disease for kinase inhibitor therapy because the majority of these tumors harbor genetic alterations that result in aberrant activation of growth factor signaling pathways. Attempts to target the Ras—Phosphatidylinositol 3-kinase (PI3K)—mammalian Target of Rapamycin (mTOR) axis in GBM with first generation receptor tyrosine kinase (RTK) inhibitors and rapalogs have been disappointing. However, there is reason for renewed optimism given the now very detailed knowledge of the cancer genome in GBM and a wealth of novel compounds entering the clinic, including next generation RTK inhibitors, class I PI3K inhibitors, mTOR kinase inhibitors (TORKinibs), and dual PI3(K)/mTOR inhibitors. This chapter reviews common genetic alterations in growth factor signaling pathways in GBM, their validation as therapeutic targets in this disease, and strategies for future clinical development of kinase inhibitors for high grade glioma.

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Acknowledgments

We thank Ms. Farzeen Aslam for secretarial assistance. This work was supported through NIH U54 CA143798 and R21 CA137896 (IKM), NIH/NS 73831 (PSM), the Leon Levy Foundation (IKM), the Doris Duke Charitable Foundation (IKM), the Sontag Foundation (IKM), the James S. McDonnell Foundation (IKM), and an Advanced Clinical Research Award in Glioma from the American Society of Clinical Oncology (IKM). TFC acknowledges funding support by Art of the Brain, the Ziering Family Foundation in memory of Sigi Ziering, the Singleton Family Foundation, the Clarence Klein Fund for Neuro-Oncology, and the John W. Carson Foundation.

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  1. Human Oncology and Pathogenesis Program, Department and Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Ingo K. Mellinghoff

  2. Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Nikolaus Schultz

  3. Department of Pathology, University of California Los Angeles, Los Angeles, CA, USA

    Paul S. Mischel

  4. Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA

    Timothy F. Cloughesy

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  1. Ingo K. Mellinghoff
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Correspondence to Ingo K. Mellinghoff .

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  1. , Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, York Avenue 1275, New York, 10065, New York, USA

    Ingo K. Mellinghoff

  2. , Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, York Avenue 1275, New York, 10065, New York, USA

    Charles L. Sawyers

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Mellinghoff, I.K., Schultz, N., Mischel, P.S., Cloughesy, T.F. (2011). Will Kinase Inhibitors Make it as Glioblastoma Drugs?. In: Mellinghoff, I., Sawyers, C. (eds) Therapeutic Kinase Inhibitors. Current Topics in Microbiology and Immunology, vol 355. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_178

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