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Early diagnosis and assignment of the most appropriate therapy pathway is therefore crucial. The KRAS/BRAF/PIK3CA Array from Randox allows the clinician to select appropriate patients for anti-EGFR therapy, maximising drug efficacy and minimising adverse side effects to the patient.
Monoclonal antibodies (MoAbs) targeting the epidermal growth receptor (EGFR) have proven effective in combination with chemotherapy or as single agents for treatment of mCRC 3,4. However, only a subset of patients with mCRC clinically benefit from EGFR-targeted moAbs.
Mutations in the KRAS gene are known to disrupt the EGFR pathway, rendering the anti-EGFR therapy ineffective. Presence of KRAS mutations accounts for approximately 35-45% of non-responsive patients5. Oncogenic mutations in genes encoding key downstream effectors within the EGFR signalling pathways may also be responsible for resistance to EGFR-targeted moAbs5. Mutations within the BRAF6 and PIK3CA7 genes have now been reported to affect patient response to EGFR-targeted moAbs.
The KRAS/BRAF/PIK3CA Array is designed for the rapid qualitative detection of point mutations within the genes KRAS, BRAF and PIK3CA from tissue DNA. The array offers a streamlined workflow, with the protocol and reagents specially optimised for the molecular laboratory and is compatible for use with a range of genomic DNA input and type including; cell lines, FFPE tissue and fresh/frozen tissue. A single DNA sample is required for testing, with results obtained in three hours. The technique of a single reaction multiplex coupled to a biochip provides greater mutation coverage of the three most important genes (KRAS, BRAF and PIK3CA) implicated in metastatic colorectal cancer therapy response. With three internal controls on each individual biochip, results are reliable.
The KRAS/BRAF/PIK3CA Array from Randox offers a rapid, reliable and simple method of selecting patients who are more likely to respond to anti-EGFR therapy, thereby allowing correct treatment to begin early, avoiding extra costs and adverse side effects associated with administrating ineffective treatment.
About Randox
Headquartered in the United Kingdom, Randox Laboratories Ltd (randox.com)is a market leader within the in vitro diagnostics industry, manufacturing high quality diagnostic products for laboratories worldwide. Our extensive product portfolio offers complete solutions within the fields of clinical chemistry, cardiology, forensic toxicology, veterinary, drug residues, life sciences, oncology, molecular diagnostics and internal and external quality control. Our goal is to ‘revolutionise healthcare through continuously improving diagnostic solutions.’ We continue to achieve this year after year due to our commitment and significant re-investment in Research and Development. Our innovative approach to diagnostics allows us to develop revolutionary products, specifically designed to provide more efficient, higher quality and reliable results, ensuring patients receive the right diagnosis at the right time.
References:
1. Ferlay, J., Autier, P, Boniol, M., et al. (2007) Estimates of the cancer incidence and mortality in Eurpe in 2006. Ann Onol 18, 581-592.
2. Centers for Disease Control and Prevention: United States Cancer Statistics: US Cancer Statistics Working Group. cdc.gov/uscs.
3. Saltz, L.B., Meropol, N.J., Loehrer, P.J. Sr, et al. (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expressed the epidermal growth factor receptor. Journal of Clinical Oncology 22, 1201-1208.
4. Cunningham, D., Humblet, Y., Siena, S., et al. (2008) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New England Journal of Medicine 358, 1160-1174.
5. Bardelli, A. & Sienna, S. (2010) Molecular Mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. Journal of Clinical Oncology 28(7) 1254-1261.
6. Di Nicolantonio, F., Martini, M., Molinari, Sartore-Bianchi, A., Arena, S., et al. (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. Journal of Clinical Oncology 26(35), 5705-5712.
7. Sartore-Bianchi, A., Martini, M., Molinari, F. et al. (2009) PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Research 69, 1851-1857.
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