What is Target GI?
As part of the Caris Dx Target Now (TM) testing program, Target GI utilizes molecular profiling techniques on formalin fixed paraffin embedded tissue, 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, only putative targets have been included for which the IBERC has determined sufficient evidence currently exists. The IBERC will be monitoring the literature and will bring you additional markers when our quality metrics are fulfilled.

Exactly what type of testing is performed with Target GI?
Target GI incorporates both IHC and mutational analysis. Specifically, Target GI includes the following:

KRAS: Recent discoveries have identified that when the KRAS gene is mutated, it 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

What are the specimen requirements for Target GI?
For the Target GI analysis, we will require the following:
     •One paraffin block or
     •Twelve (12) unstained slides
            -Seven (7) unstained and positively charged for IHC
            -Five (5) unstained and uncharged for KRAS mutational analysis

All biopsies must have some tumor present in the deeper sections of the paraffin block used for IHC analysis. Blocks will always be returned in a timely fashion, as requested.

All samples must be submitted with the corresponding pathology report. The stated diagnoses are confirmed via light microscopy that tumor is present.

How do I order Target GI?
Please contact us at 800-901-5177 and inquire about Target GI ordering information. For timely results, please do not ship on the day prior to a major holiday.

What type of report will I receive?
Target GI results are integrated in an easy to interpret informational report. Each report provides a unique and detailed molecular snapshot of a patient’s tumor characterization based on the immunoreactivity and mutational status of the markers tested. The report also includes information on the therapeutic impact of these markers in colorectal cancer based upon the scientific literature, with an assessment of the Literature Level of Evidence as determined by the Caris Dx Interdisciplinary Biomarker Evidence Review; however the decision about how to treat any patient is the responsibility of their physician.

What is the turnaround time for Target GI testing?
Once we receive the tissue specimens, required forms, and medical information, analysis takes approximately seven (7) business days.

Is Target GI reimbursed?
The Target GI test is reimbursed by Medicare and other third-party payors. Caris Dx will bill third party payors for Target GI testing and there are no out-of-pocket costs for the patient, except for co-pays or deductibles as required by law or the patient’s insurance plan.

Will my office need to obtain prior authorization from the patient’s insurance company prior to Target GI testing?
If required, prior authorization should be obtained before submitting a specimen. Caris Dx can help you obtain this information.

Who do I call for additional information or with questions on Target GI?
Please call us at 800-901-5177

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