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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Decreasing relapse in colorectal cancer patients treated with cetuximab by using the activating KRAS detection chip
Ming-Yii Huang1, Hsueh-Chiao Liu, Li-Chen Yen
1Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Abstract:
The KRAS oncogene was among the first genetic alterations in colorectal cancer (CRC) to be discovered. Moreover, KRAS somatic mutations might be used for predicting the efficiency of anti-epidermal growth factor receptor therapeutic drugs. Because the KRAS mutations are similar in the primary CRC and/or the CRC metastasis, KRAS mutation testing can be performed on both specimen types. The purpose of this study was to investigate the clinical advantage of using a KRAS pathway-associated molecule analysis chip to analyze CRC patients treated with cetuximab. Our laboratory developed a KRAS pathway-associated molecule analysis chip and a weighted enzymatic chip array (WEnCA) technique, activating KRAS detection chip, which can detect KRAS mutation status by screening circulating cancer cells in the bloodstream. We prospectively enrolled 210 stage II-III CRC patients who received adjuvant oxaliplatin plus infusional 5-fluorouracil/leucovorin (FOLFOX)-4 chemotherapy with or without cetuximab. We compared the chip results of preoperative blood specimens with disease control status in these patients. Among the 168 CRC patients with negative chip results, 119 were treated with FOLFOX-4 plus cetuximab chemotherapy, and their relapse rate was 35.3 % (42/119). In contrast, the relapse rate was 71.4 % among the patients with negative chip results who received FOLFOX-4 treatment alone (35/49). Negative chip results were significantly correlated with better treatment outcomes in the FOLFOX-4 plus cetuximab group (P < 0.001). We suggest that the activating KRAS detection chip is a potential tool for predicting clinical outcomes in CRC patients following FOLFOX-4 treatment with or without cetuximab therapy.
Insights
A novel KRAS detection chip accurately predicts colorectal cancer (CRC) treatment outcomes. Negative chip results in patients receiving cetuximab with chemotherapy indicated significantly lower relapse rates, suggesting its clinical utility.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Therapeutics
Background:
- KRAS oncogene mutations are early genetic alterations in colorectal cancer (CRC).
- KRAS mutation status is crucial for predicting the efficacy of anti-epidermal growth factor receptor (EGFR) therapies.
- KRAS mutations are consistent between primary CRC and metastases, allowing testing on various specimen types.
Purpose of the Study:
- To evaluate the clinical utility of a KRAS pathway-associated molecule analysis chip for CRC patients treated with cetuximab.
- To assess the predictive value of a novel KRAS detection chip using circulating tumor cells.
Main Methods:
- Development of a KRAS pathway-associated molecule analysis chip and a weighted enzymatic chip array (WEnCA) technique.
- Prospective enrollment of 210 stage II-III CRC patients receiving FOLFOX-4 chemotherapy with or without cetuximab.
- Analysis of preoperative blood specimens to correlate chip results with disease control status.
Main Results:
- Among 168 patients with negative chip results, those treated with FOLFOX-4 plus cetuximab had a 35.3% relapse rate versus 71.4% for FOLFOX-4 alone.
- Negative chip results were significantly associated with better treatment outcomes in the cetuximab combination therapy group (P < 0.001).
Conclusions:
- The activating KRAS detection chip shows potential as a predictive tool for clinical outcomes in CRC patients.
- This chip may aid in tailoring treatment strategies, particularly for patients receiving FOLFOX-4 with or without cetuximab.
