KRAS / BRAF / PIK3CA Array*
The KRAS / BRAF / PIK3CA Array* provides rapid detection of mutations within KRAS, BRAF and PIK3CA genes, enabling appropriate selection of patients for anti-EGFR therapy.
Colorectal cancer (CRC) is the third most common cancer worldwide 1. Metastatic disease accounts for 40-50% of newly diagnosed patients and is associated with high morbidity 1, 2. Despite recent therapeutic advances, the prognosis for patients with metastatic CRC (mCRC) remains poor 3. Early treatment is therefore critical. This array allows the clinician to correctly select appropriate patients for anti-EGFR therapy, thereby maximising drug efficacy and minimising adverse side effects to the patient.
Monoclonal antibodies (MoAbs) targeting the epidermal growth factor receptor (EGFR) have proven effective in combination with chemotherapy or as single agents for treatment of mCRC 4, 5. These molecules bind to the extracellular domain of EGFR with high affinity and competitively inhibit ligand binding, which leads to inhibition of phosphorylation and subsequent activation of downstream signalling pathways. 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 anti-EGFR therapy ineffective. Presence of KRAS mutations accounts for approximately 35-45% of non-responsive patients3. Oncogenic mutations in genes encoding key downstream effectors within the EGFR-signalling pathways may also be responsible for resistance to EGFR-targeted MoAbs6. Mutations within the BRAF 7 and PIK3CA 8 genes have now been reported to affect patient response to EGFR-targeted MoAbs.
- Streamlined workflow – Protocol and reagents are optimised for the molecular laboratory
- Compatible with a broad range of genomic DNA input and type:
- Cell lines
- FFPE tissue
- Fresh/frozen tissue
- Detection of 1% mutant in a background of wildtype genomic DNA
- Single DNA sample (100 ng total) only required
- Single reaction multiplex PCR 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.
- Turnaround time of three hours
- 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.
- Centers for Disease Control and Prevention: United States Cancer Statistics: US Cancer Statistics Working Group. http://www.cdc.gov/uscs.
- Bardelli, A. & Sienna, S. (2010) Molecular Mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. Journal of Clinical Oncology 28(7) 1254-1261.
- 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.
- 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.
- De Rook, W., De Vriendt, V., Normanno, N., et al. (2011) KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncology12(6) 594-603.
- 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.
- 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.
*PIK3CA for research use only.