Target GI: Providing the information you need to tailor individual therapy for your colorectal cancer patient

As part of the Caris Dx Target Now (TM) testing program, Target GI utilizes molecular profiling techniques, including mutational analysis and immunohistochemistry (IHC) to provide information on key molecular targets that are relevant to the clinical management of colorectal cancer patients.

Built on an exceptionally robust literature review process with a framework adopted from the US Preventive Services Task Force1, our Interdisciplinary Biomarker Evidence Review Committee (IBERC) selects and summarizes the most significant and relevant scientific material to support the chosen Target GI biomarkers and their potential therapeutic implications. Importantly, many putative targets are not included for which our IBERC has determined that currently insufficient evidence exists that warrants it inclusion.

Target GI Analysis Includes:

KRAS: Recent discoveries have identified that when the KRAS gene is mutated, confers resistance to cetuximab (ERBITUX®) and panitumumab (Vectibix®) in colorectal cancer patients by circumventing EGFR’s role in the signaling pathway. The Caris Dx KRAS assay is a comprehensive mutational analysis using DNA sequencing that detects 99% of known mutations.2,3,4,5

Topoisomerase 1 (TOPO1): Topoisomerase 1 (TOPO1) is an enzyme involved in the replication and transcription of DNA. Certain drugs of the captothecin family including irinotecan (Camptosar®) and topotecan (Hycamtin®) have been shown to directly target TOPO1 in colon cancer.6

Thymidylate Synthase (TS): Many other pathways are involved in the growth of cancer. The enzyme thymidylate synthase is involved in the production of the DNA base thymidine. The scientific literature indicates that treatment with either fluorouracil (ADRUCIL®, Efudex®, FLUOROPLEX®) or capecitabine (Xeloda®) is less effective for colon cancer patients over-expressing the TS marker.7, 8

Target GI Facts regarding Colorectal Cancer:

• KRAS mutation status is critical for the identification of patients that will likely be non-responsive to EGFR targeted therapy
• TOPO1 levels were recently found to be associated with a survival benefit for patients treated with irinotecan
• Increased expression of TS has been associated with lack of response to fluorouracil-based chemotherapy

Caris Dx Target GI:

• Provides vital information to help tailor individualized therapy for your patient
• Testing is performed on archived specimens (fixed, paraffin blocks)
• Tumor specimens submitted for full analysis should contain a minimum of >2 mm diameter of 100% tumor or 4 mm of 50% tumor or an equivalent combination (required for mutational analysis)
• 7 day turn around
  

REFERENCES:
1. Harris, T., D. Atkins, et al. (2001). “Current Methods of the U.S. Preventive Services Task Force.” Am J Prev Med 20(3S)
2. Amado, R.G., et al., Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol, 2008. 26(10): p. 1626-34.
3. De Roock, W., et al., KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol, 2008. 19(3): p. 508-15.
4. Khambata-Ford, S., et al., Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol, 2007. 25(22): p. 3230-7.
5. Di Fiore, F., et al., Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer, 2007. 96(8): p. 1166-9.
6. Braun, M.S., et al., Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. J Clin Oncol, 2008. 26(16): p. 2690-8.
7. Cascinu, S., et al., Vascular endothelial growth factor expression, S-phase fraction and thymidylate synthase quantitation in node-positive colon cancer: relationships with tumor recurrence and resistance to adjuvant chemotherapy. Ann Oncol, 2001. 12(2): p. 239-44.
8. Ciaparrone, M., et al., Predictive role of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer patients receiving adjuvant 5-fluorouracil. Oncology, 2006. 70(5): p. 366-77.

ERBITUX® is a registered trademark of ImClone Systems Incorporated
Vectibix® is a registered trademark of Amgen Incorporated
Camptosar® is a registered trademark of Pfizer
Hycamtin® is a registered trademark of GlaxoSmithKline
ADRUCIL® is a registered trademark of Teva Pharmaceuticals USA
Efudex® is a registered trademark of Valeant Pharmaceuticals International
FLUOROPLEX® is a registered trademark of Allergan Incorporated
Xeloda® is a registered trademark of Roche Pharmaceuticals