TheraScreen: K-RAS

Mutations in the K-RAS oncogene are frequently found in human cancers. They are common in colorectal cancer, pancreatic cancer, lung adenocarcinoma, gall bladder cancer, bile duct cancer and thyroid cancer. These mutations can indicate prognosis and may be predictive of drug response. In particular, recent publications have shown that the successful treatment of metastatic Colorectal Cancer (mCRC), using monoclonal antibody therapies such as Panitumumab (Amgen) or Cetuximab (Erbitux, Merck), is directly linked to the oncogenic activation of the KRAS signalling pathway. (1-6).

TheraScreen LogoRecently the European Commission has granted a conditional marketing authorization for Vectibix® (panitumumab) as monotherapy for the treatment of patients with epidermal growth factor receptor (EGFR) expressing metastatic colorectal cancer (mCRC) with non-mutated (wild-type) KRAS genes after failure of standard chemotherapy regimens. Vectibix has been granted a positive Commission decision in the European Union (EU) based upon a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) for marketing authorization in September of this year. This approval is based on a positive benefit / risk assessment in a patient population that currently has few treatment options available to them. As part of the CHMP review, clinical data supporting the utility of KRAS mutation status as a biomarker for clinical outcome were provided.

The DxS KRAS Kit is highly selective and robust, detecting the 7 key mutations in the K-RAS gene. DxS assays employ a real-time PCR format combining Scorpions® and ARMS® (allele specific PCR) technologies. These assays can detect <1% of mutant in a background of wild type genomic DNA and have a limit of detection of 10 copies or below.

The DxS KRAS Kit can thus provide an accurate determination of the mutation status of a patient. It is available as a CE marked diagnostic from January 2008.

The TheraScreen: K-RAS Kit is not intended for use to screen for or diagnose cancer.  Its use is intended as an adjunct to other prognostic factors currently used to select suitable patients for treatment with tyrosine kinase inhibitor therapies, based on the patient’s mutation status. The patient’s mutation status will be considered by a Clinician, alongside other disease factors to make a therapy decision. No treatment decision for cancer patients should be based on EGFR gene mutation status alone.

 

How the Kit Works

This kit is a CE marked diagnostic product for professional use only.


Intended Use

To aid doctors to identify colorectal cancer patients more likely to benefit from anti-EGFR therapies such as panitumumab. 
 

K-RAS Mutations

The DxS kit detects the following mutations against a background of wild type genomic DNA in a real time PCR assay:

  1. Gly12Asp (GGT>GAT)
  2. Gly12Ala (GGT>GCT)
  3. Gly12Val (GGT>GTT)
  4. Gly12Ser (GGT>AGT)
  5. Gly12Arg (GGT>CGT)
  6. Gly12Cys (GGT>TGT)
  7. Gly13Asp (GGC>GAC)


 

Kit Attributes:

  • Maximises patient selection of likely responders by identifying mutation positive patients, frequently missed by other methods
  • Depending on the total amount of DNA present, the kit can detect 1% of mutant in a background of wild type genomic DNA. The assays have a limit of detection of 10 copies or below. These sensitivity and detection levels are superior to commonly used methods such as sequencing.
  • Simple and easy to follow protocol, with same day results.
  • Sample types include DNA from plasma or fresh, frozen or paraffin embedded tissue (PET).
  • Kit combines two technologies, ARMS® (allele specific PCR) and Scorpions® to detect mutations in real-time PCR reactions.
  • Qualitative assessment of patient mutation status; accurately detects SNPs, insertions and deletions.
  • Compatible with most real-time PCR instruments.

 
Simple Workflow:

Time to result

Detection of low level mutations (<10%)

Fragmented DNA

 Work Flow

TheraScreen Diagnostic Kit

< 5 hours

Yes

+++

 Simple

DNA Sequencing

 > 8 hours

No

+

 Complex

 

 

 

 

How to Order

Please quote the product code and kit size when you order:
Product Code:           KR-21     - 20 reaction kit
Product Code:           KR-22     - 80 reaction kit

To place an order please email sales@dxsgenotyping.com or call +44 161 606 7201

 

References

  1. E. Massarelli, M. Varella-Garcia, X. Tang, A. C. Xavier et al. (2007). KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. Clin Cancer Res 2007; 13 (10).

  2. William Pao, Theresa Y. Wang, Gregory J. Riely, Vincent A. Miller, Qiulu Pan, Marc Ladanyi et al. (2005). KRAS mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib.  PloS Medicine 2(1): 57-61.

  3. D. A. Eberhard, B. E. Johnson, L.C. Amler, A. D. Goddard et al (2005). Mutations in the EGFR and in K-RAS are predictive and prognostic indicators in patients with NSCLC treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23: 5900-5909.

  4. L. Toschi & F. Cappuzzo. (2007) Understanding the new genetics of responsiveness to EGFR tyrosine kinase inhibitors. Oncologist 12; 211-220.

  5. Sae-Won Han, Tae-You Kim, Yoon Kyung Jeon, Pil Gyu Hwang et al. (2006). Optimization of Patient Selection for Gefitinib in Non-Small Cell Lung Cancer by combined analysis of Epidermal Growth Factor Receptor Mutation, K-RAS Mutation, and AKT Phosphorylation.  Clin Cancer Res 12(8):2538-2544.

  6. Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C et al. (1989). Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) Nucleic Acids Res. 17 (7): 2503-16.

 
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