Response DX is a test that evaluates several biomarkers in colon cancer tissues, so that they can be used to design treatment. Since the EGRF and KRAS on the panel are medically necessary, I consider only these tests medically necessary. The client may consider negotating the total price for the panel based on the two medically necessary components.The test in question is actually a panel of predictive markers. They include markers that are generally accepted, for example EGFR ande KRA as well as markers that are still considered experimental for decision making, such as TS, ERCC1, BRAF, KRAS.
A little clinical information about these tests based on the information from the ResponseGenetics website:
The epidermal growth factor receptor (EGFR; ErbB-1; HER1) is a critical part of the signal transduction pathway that controls cell growth and is often over-expressed (amplified) in tumors. In a study evaluating 8 different genes as predictive factors for first-line CPT-11-based chemotherapy in colorectal cancer patients, a high intratumoral gene expression levels of EGFR was shown to be the most important factor in distinguishing responders from non-responders.
KRAS is also a part of defintion of the FDA’s approval for use of Erbitux. KRAS, a vital member of the signal transduction pathways that regulate cell growth, is often mutated in tumors. KRAS, a vital member of the signal transduction pathways that regulate cell growth, is often mutated in tumors. Mutations in KRAS gene preclude response to EGFR-directed tyrosine kinase inhibitors (TKI) but not all tumors with wild-type KRAS will respond either.The presence of KRAS mutations, which occur predominantly in patients who are current or past smokers, is strongly associated with a lack of response of CRC to the anti-EGFR antibody cetuximab. Three independent studies reported response rates of 0% to cetuximab among patients with mutated KRAS as well as shorter overall survival.
The enzyme excision repair complementing factor 1 (ERCC1) is part of the pathway that repairs DNA damage caused by platin therapy. Low ERCC1 has consistently been found in several retrospective studies to be a favorable indicator for response of tumors and/or improved survival after platinum therapy while high ERCC1 expression is associated with resistance to platinum therapy and shorter survival in many cancer types including gastric, ovarian, bladder, head-and-neck, non-small cell lung, esophageal and colorectal. In a study of advanced colorectal cancer study treated with 5-FU/oxaliplatin,1 low ERCC1 mRNA expression levels were significantly associated with longer survival. In contrast to oxaliplatin regimens, high expression of ERCC1 was correlated with response to irinotecan therapy.
Thymidylate synthase (TS) is a growth rate-limiting enzyme of DNA synthesis. TS expression is a predictor of response to 5-fluorouracil (5-FU), which for over 50 years has been a mainstay of chemotherapy of colorectal cancer (CRC). Many studies have agreed that high levels of TS are associated with resistance of tumors to 5-FU and its derivatives, even when used in combination with other agents such as oxaliplatin (the FOLFOX regimen).
Shirota Y, Stoehlmacher J, Brabender J, et al, ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy: J Clin Oncol. 2001;19:4298-4304.
Vallboehmer D, Iqbal S, Yang DY, et al. Molecular determinants of irinotecan efficacy, Int J Cancer. 2006;119:2435-2442.
Cobo M, Isla D, Massuti B, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007;25:2747-2754.