Summary
Tumor-specific and germ-line variations of DNA significantly contribute to tumor growth and its ability to develop resistance. Among several mechanisms that cause resistance to cancer treatment, the genotype of certain growth factors, like epidermal growth factor receptor (EGFR), is critical. EGFR signals requests for proliferation and survival toward the nucleus of the cancer cell. Several polymorphic DNA sequences of EGFR and the mutational status of the Kirsten-Ras (KRAS) gene appear to be determinants of response to new drugs that inhibit EGFR. We describe the correlation between the EGFR genotype, including the KRAS mutation, and the consequences of the resulting genotype for anti-EGFR therapy in colorectal cancer.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
McLeod H. (2006) Individualizing cancer chemotherapy. Clin Adv Hematol Oncol. 4(4), 259–61.
Evans W. E., and Relling M. V. (2004) Moving towards individualized medicine with pharmacogenomics. Nature 429, 464–8.
Overmann M. J., and Hoff P. M. (2007) EGFR-targeted therapies in colorectal cancer. Dis Colon Rectum 50, 1259–70.
Reuter C. W., Morgan M. A., and Eckardt A. (2007) Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck. Br J Cancer 96, 408–16
Gebhardt F., Bürger H., and Brandt B. (2000) Modulation of EGFR gene transcription by secondary structures, a polymorphic repetitive sequence and mutations - a link between genetics and epigenetics. Histol Histopathol 15, 929–36
McCubrey J. A., Steelman L. S., Chappell W. H., Abrams S. L., Wong E. W., Chang F., et al. (2007) Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773, 1263–84.
Lievre A., Bachet J. B., LeCorre D., Boige V., Laudi B., Emile J. F., et al. (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66, 3992–5.
Amado R. G., Wolf M., Freeman D., Peeters M., Van Cutsem E., Siena S., et al. (2007) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer: results from a randomized, controlled trial. ECCO 2007, LBA#7.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Mogck, U., Goekkurt, E., Stoehlmacher, J. (2009). The EGFR Pathway as an Example for Genotype: Phenotype Correlation in Tumor Genes. In: Grützmann, R., Pilarsky, C. (eds) Cancer Gene Profiling. Methods in Molecular Biology, vol 576. Humana Press. https://doi.org/10.1007/978-1-59745-545-9_17
Download citation
DOI: https://doi.org/10.1007/978-1-59745-545-9_17
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-934115-76-3
Online ISBN: 978-1-59745-545-9
eBook Packages: Springer Protocols