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KRAS testing in metastatic colorectal cancer: implications on the use of biologic agents
1Department of Medicine, Division of Hematology and Oncology, The Ohio State University-Arthur James Cancer Hospital, Columbus, OH 43210-1240, USA. tanios.bekaii-saab@osumc.edu
Abstract:
Colorectal cancer is a significant healthcare problem in the United States, with meaningful improvement in survival over the past few years. Much of that improvement is attributable to the availability of molecularly targeted therapies, such as inhibitors of the vascular endothelial growth factor (bevacizumab) and epidermal growth factor receptor (cetuximab and panitumumab), in addition to active cytotoxic agents. KRAS mutations have long been described to play an adverse prognostic role in colorectal cancer. KRAS is downstream from EGFR, and oncogenic mutations will yield a constitutively active protein that will override EGFR control of downstream signaling. Such mutations in KRAS would therefore confer resistance to anti-EGFR antibodies. The cumulative results of several trials incorporating more than a thousand patients in studies of cetuximab and panitumumab confirm that the presence of KRAS mutation in tumors is highly predictive of resistance to anti-EGFR therapy. These findings are likely to change the landscape of metastatic CRC treatment by providing an improved patient-tailored approach.
Insights
KRAS mutations in colorectal cancer predict resistance to epidermal growth factor receptor (EGFR) therapies like cetuximab. Identifying these mutations allows for personalized treatment strategies, improving patient outcomes in metastatic CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) presents a significant health challenge in the United States.
- Survival rates have improved due to targeted therapies like vascular endothelial growth factor inhibitors and epidermal growth factor receptor (EGFR) inhibitors.
- KRAS mutations are known to have a negative prognostic role in CRC.
Purpose of the Study:
- To investigate the predictive value of KRAS mutations for resistance to anti-EGFR therapies in colorectal cancer patients.
- To evaluate the impact of KRAS mutation status on treatment response to cetuximab and panitumumab.
Main Methods:
- Analysis of cumulative results from several clinical trials involving over a thousand patients.
- Assessment of tumor KRAS mutation status in relation to response to anti-EGFR antibodies (cetuximab and panitumumab).
Main Results:
- The presence of KRAS mutations in tumors was confirmed to be highly predictive of resistance to anti-EGFR therapy.
- Patients with KRAS mutations did not benefit from cetuximab and panitumumab treatment, indicating a lack of efficacy.
Conclusions:
- KRAS mutation testing is crucial for guiding treatment decisions in metastatic colorectal cancer.
- Identifying KRAS mutations enables a more tailored, patient-specific approach to CRC therapy, optimizing treatment selection and improving survival.
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