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. 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 patients. Oncogenic mutations in genes encoding key downstream effectors within the EGFR signalling pathways may also be responsible for resistance to EGFR-targeted moAbs. Mutations within the BRAF and PIK3CA 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.  

For more information contact us at marketing@randox.com

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. http://www.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.