The treatment of colorectal carcinoma with monoclonal antibodies: the importance of KRAS mutation analysis and EGFR status.
BACKGROUND
The epidermal growth factor receptor (EGFR) is an important target in the treatment of metastatic colorectal carcinoma (mCRC). The combination of anti-EGFR antibodies with chemotherapy has led to a higher response rate of certain kinds of tumor as well as a significant prolongation of the progression-free interval. The KRAS protein is an important mediator in the signal transduction cascade regulated by the EGFR. A KRAS mutation is present in 30% to 49% of all colorectal carcinomas. Mutations in the KRAS gene can be demonstrated by the methods of molecular pathology and are a very important factor in the selection of molecular biological treatment options targeted against EGFR.


METHODS
Selective literature review.


RESULTS
Patients bearing mutations of the KRAS gene do not benefit from treatment with the EGFR antibodies cetuximab and panitumumab.


CONCLUSIONS
Activating mutations of the KRAS gene are biomarkers for resistance to cetuximab or panitumumab. Thus, anti-EGFR therapies are approved for the treatment of metastatic colorectal carcinoma only on condition that the mutation state of the KRAS gene is determined first, because the combination of chemotherapy with anti-EGFR is expected to increase the response rate only in patients with the wild-type KRAS gene.
Stintzing
Sebastian
S
Medizinische Klinik und Poliklinik III, Klinikum der LMU München, München, Germany.
Heinemann
Volker
V
Moosmann
Nicolas
N
Hiddemann
Wolfgang
W
Jung
Andreas
A
Kirchner
Thomas
T
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004252:DNA Mutational Analysis; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009154:Mutation / Q000235:genetics; D018579:Patient Selection; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins