TY - JOUR
T1 - Biomarkers of resistance to epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer
AU - Banck, Michaela S.
AU - Grothey, Axel
PY - 2009/12/15
Y1 - 2009/12/15
N2 - Genomics and proteomics have held out the promise of individualized medicine for the last 10 or 20 years, but clinical medicine has not yet delivered on this promise. Some cancers, such as breast cancer and some hematologic malignancies, have been at the forefront of individualized therapeutic approaches by integrating molecular biomarkers into treatment decision algorithms. Until recently, the treatment of colorectal cancer (CRC) has lagged behind these other cancers in this regard and therapeutic decisions have been solely empirical. Data from various clinical trials and translational studies have now opened the door for individualized treatment approaches by identifying patients with metastatic CRC who are most likely to benefit from antibodies against the epidermal growth factor receptor (EGFR), cetuximab and panitumumab. Activating mutations of KRAS, a downstream mediator of EGFR signaling, has been shown to render EGFR antibodies ineffective, such that analyzing tumors for these mutations has become mandatory before the use of EGFR antibodies is considered in CRC. Beyond KRAS, several additional biomarkers are currently being investigated as potential positive or negative predictors for the efficacy of EGFR-targeted therapy. Most of these markers are alterations of molecules integrated in the EGFR pathway. This review will focus on the type and quality of evidence that has been gathered to date to predict resistance to monoclonal antibodies against EGFR in CRC.
AB - Genomics and proteomics have held out the promise of individualized medicine for the last 10 or 20 years, but clinical medicine has not yet delivered on this promise. Some cancers, such as breast cancer and some hematologic malignancies, have been at the forefront of individualized therapeutic approaches by integrating molecular biomarkers into treatment decision algorithms. Until recently, the treatment of colorectal cancer (CRC) has lagged behind these other cancers in this regard and therapeutic decisions have been solely empirical. Data from various clinical trials and translational studies have now opened the door for individualized treatment approaches by identifying patients with metastatic CRC who are most likely to benefit from antibodies against the epidermal growth factor receptor (EGFR), cetuximab and panitumumab. Activating mutations of KRAS, a downstream mediator of EGFR signaling, has been shown to render EGFR antibodies ineffective, such that analyzing tumors for these mutations has become mandatory before the use of EGFR antibodies is considered in CRC. Beyond KRAS, several additional biomarkers are currently being investigated as potential positive or negative predictors for the efficacy of EGFR-targeted therapy. Most of these markers are alterations of molecules integrated in the EGFR pathway. This review will focus on the type and quality of evidence that has been gathered to date to predict resistance to monoclonal antibodies against EGFR in CRC.
UR - http://www.scopus.com/inward/record.url?scp=73349091211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73349091211&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-09-0188
DO - 10.1158/1078-0432.CCR-09-0188
M3 - Review article
AN - SCOPUS:73349091211
SN - 1078-0432
VL - 15
SP - 7492
EP - 7501
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -