Az epidermális növekedési faktor recept orát célzó terápiák RAS paradoxona vastag- és végbélrákban

Translated title of the contribution: The RAS paradoxon of the EGFR-targeted therapy of colorectal cancer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

During the carcinogenesis of colorectal cancer in about half of the cases K-RAS, while much less frequently B-RAF mutation occur in early adenomas. While K-RAS mutant tumors are more likely present in male patients, B-RAF mutant tumors develop more frequently in females and are independent of the microsatellite status. Colorectal cancers are characterized by EGFR expression; the gene is not mutated, rarely amplified and increased copy number is due to chromosomal polysomy. This pheno-/genotype of colorectal cancer lent support to the introduction of anti-EGFR antibody therapies. For a while positive EGFR expression status of the tumor was the basis of patient selection for these targeted therapies in colorectal cancer. Monotherapies with the two available anti-EGFR antibodies of chemoresistant colorectal cancers resulted in appr. 10% objective response rate, which was independent of the level of EGFR expression. In case of panitumumab it was discovered that the efficacy of this targeted therapy depends on the K-RAS mutant status of the tumors. Furthermore, preliminary data suggest that cetuximab combined with chemotherapy is effective also exclusively in K-RAS wild-type tumors. Based on these data it is safe to say that K-RAS mutant status of colorectal cancer is a negative predictor for EGFR-targeted therapies of colorectal cancer. Accordingly, it is necessary to determine the K-RAS status of colorectal cancer before making therapeutic decisions.

Original languageHungarian
Pages (from-to)185-191
Number of pages7
JournalMagyar Onkologia
Volume52
Issue number2
DOIs
Publication statusPublished - 2008

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Colorectal Neoplasms
Therapeutics
Neoplasms
Anti-Idiotypic Antibodies
Adenoma
Microsatellite Repeats
Patient Selection
Decision Making
Carcinogenesis
Genotype
Drug Therapy
Mutation
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "Az epiderm{\'a}lis n{\"o}veked{\'e}si faktor recept or{\'a}t c{\'e}lz{\'o} ter{\'a}pi{\'a}k RAS paradoxona vastag- {\'e}s v{\'e}gb{\'e}lr{\'a}kban",
abstract = "During the carcinogenesis of colorectal cancer in about half of the cases K-RAS, while much less frequently B-RAF mutation occur in early adenomas. While K-RAS mutant tumors are more likely present in male patients, B-RAF mutant tumors develop more frequently in females and are independent of the microsatellite status. Colorectal cancers are characterized by EGFR expression; the gene is not mutated, rarely amplified and increased copy number is due to chromosomal polysomy. This pheno-/genotype of colorectal cancer lent support to the introduction of anti-EGFR antibody therapies. For a while positive EGFR expression status of the tumor was the basis of patient selection for these targeted therapies in colorectal cancer. Monotherapies with the two available anti-EGFR antibodies of chemoresistant colorectal cancers resulted in appr. 10{\%} objective response rate, which was independent of the level of EGFR expression. In case of panitumumab it was discovered that the efficacy of this targeted therapy depends on the K-RAS mutant status of the tumors. Furthermore, preliminary data suggest that cetuximab combined with chemotherapy is effective also exclusively in K-RAS wild-type tumors. Based on these data it is safe to say that K-RAS mutant status of colorectal cancer is a negative predictor for EGFR-targeted therapies of colorectal cancer. Accordingly, it is necessary to determine the K-RAS status of colorectal cancer before making therapeutic decisions.",
keywords = "Antibody therapy, Colorectal cancer, EGFR, K-RAS",
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T1 - Az epidermális növekedési faktor recept orát célzó terápiák RAS paradoxona vastag- és végbélrákban

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AU - Láng, I.

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N2 - During the carcinogenesis of colorectal cancer in about half of the cases K-RAS, while much less frequently B-RAF mutation occur in early adenomas. While K-RAS mutant tumors are more likely present in male patients, B-RAF mutant tumors develop more frequently in females and are independent of the microsatellite status. Colorectal cancers are characterized by EGFR expression; the gene is not mutated, rarely amplified and increased copy number is due to chromosomal polysomy. This pheno-/genotype of colorectal cancer lent support to the introduction of anti-EGFR antibody therapies. For a while positive EGFR expression status of the tumor was the basis of patient selection for these targeted therapies in colorectal cancer. Monotherapies with the two available anti-EGFR antibodies of chemoresistant colorectal cancers resulted in appr. 10% objective response rate, which was independent of the level of EGFR expression. In case of panitumumab it was discovered that the efficacy of this targeted therapy depends on the K-RAS mutant status of the tumors. Furthermore, preliminary data suggest that cetuximab combined with chemotherapy is effective also exclusively in K-RAS wild-type tumors. Based on these data it is safe to say that K-RAS mutant status of colorectal cancer is a negative predictor for EGFR-targeted therapies of colorectal cancer. Accordingly, it is necessary to determine the K-RAS status of colorectal cancer before making therapeutic decisions.

AB - During the carcinogenesis of colorectal cancer in about half of the cases K-RAS, while much less frequently B-RAF mutation occur in early adenomas. While K-RAS mutant tumors are more likely present in male patients, B-RAF mutant tumors develop more frequently in females and are independent of the microsatellite status. Colorectal cancers are characterized by EGFR expression; the gene is not mutated, rarely amplified and increased copy number is due to chromosomal polysomy. This pheno-/genotype of colorectal cancer lent support to the introduction of anti-EGFR antibody therapies. For a while positive EGFR expression status of the tumor was the basis of patient selection for these targeted therapies in colorectal cancer. Monotherapies with the two available anti-EGFR antibodies of chemoresistant colorectal cancers resulted in appr. 10% objective response rate, which was independent of the level of EGFR expression. In case of panitumumab it was discovered that the efficacy of this targeted therapy depends on the K-RAS mutant status of the tumors. Furthermore, preliminary data suggest that cetuximab combined with chemotherapy is effective also exclusively in K-RAS wild-type tumors. Based on these data it is safe to say that K-RAS mutant status of colorectal cancer is a negative predictor for EGFR-targeted therapies of colorectal cancer. Accordingly, it is necessary to determine the K-RAS status of colorectal cancer before making therapeutic decisions.

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