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Targeted Therapies pp 171–195Cite as

Rational Combination of Targeted Agents to Overcome Cancer Cell Resistance

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

Abstract

The introduction of targeted agents such as the Bcr/Abl kinase inhibitor – imatinib mesylate – into the therapeutic armamentarium has revolutionized chemotherapeutic approaches to neoplastic diseases. However, as in the case of conventional chemotherapeutic agents, resistance mechanisms, either preexisting or those that develop following treatment, have limited the therapeutic potential of such agents. Over the last decade, it has become increasingly clear that survival signaling pathways do not exist in a vacuum, but instead exhibit strong evidence of cross-talk and mutual interdependence. In addition, a substantial body of evidence indicates that multiple dysregulated survival pathways may cooperate to trigger transformation. Such considerations raise the possibility that simultaneous interruption of more than one signaling pathway may represent an effective anticancer strategy. Indeed, numerous studies have now demonstrated that because many cancer cell types are not addicted to a single such pathway, simultaneous interruption of a constitutively activated and stimulated complementary pathway may effectively induce transformed cell death. Furthermore, this strategy may be particularly effective in the case of resistant disease. This chapter summarizes mechanisms of tumor cell resistance to novel agents, and provides examples of rational combination approaches involving targeted agents that might circumvent this problem.

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Acknowledgments

This work was supported by awards CA63753, CA93738, CA100866, and P50CA130805 from the National Institutes of Health; award R6059-06 from the Leukemia and Lymphoma Society of America; Lymphoma SPORE award P50CA130805; and an award from the V Foundation.

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  1. Department of Internal Medicine, Hematology/Oncology, Virginia Commonwealth University, Richmond, VA, USA

    Steven Grant

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  1. Yun Dai
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Correspondence to Steven Grant .

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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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Dai, Y., Grant, S. (2011). Rational Combination of Targeted Agents to Overcome Cancer Cell Resistance. In: Gioeli, D. (eds) Targeted Therapies. Molecular and Translational Medicine. Humana Press. https://doi.org/10.1007/978-1-60761-478-4_10

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  • DOI: https://doi.org/10.1007/978-1-60761-478-4_10

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