Translation of TempO-Dx Expanded RASRAF Test markers onto liquid biopsy platform for monitoring treatment resistance in colorectal cancer

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Precision medicine approaches align available therapies with patients' biology in order to provide the most suitable treatments for specific disease cases. In colorectal cancer, treatments are often prescribed which target EGFR, a biomarker present on the cell surface of cells. However, if a patients' tumour harbours certain mutations in the genes KRAS, NRAS and BRAF, EGFR therapy will be ineffective. Therefore, determination of the tumour mutation status in colorectal cancer is essential to advise clinicians of the best course of treatment. This improves patient outcomes by allowing them quicker access to the most relevant therapies, avoids unnecessary side effects and prevents patients being given expensive unsuccessful treatments.However, patients who are initially eligible for anti-EGFR therapies are known to develop acquired resistance to these treatments in the majority of cases. Anti-EGFR resistance can be caused by the tumour evolving mutations in the genes described above. Therefore, continued monitoring of the mutational status of these patients is essential. At present, treatment is continued until the patient shows signs of disease progression, meaning that patients face a delay in being offered alternative treatment which may affect patient outcomes as treatment is continued with potential unpleasant side effects and results in costly treatment being given with no effect.Effective monitoring of patients' mutational status throughout their disease progression is therefore essential. The current gold standard for KRAS, NRAS and BRAF testing at diagnosis and throughout disease is via tissue biopsies, which are invasive and unpleasant for patients. Access to additional tissue biopsies beyond the initial diagnosis, is not always possible and this poses a challenge to continued monitoring of patients.We aim to develop an innovative liquid biopsy-based test to determine and monitor patients' RASRAF gene mutation status. BioClavis has developed a more efficient test based on the TempO-Dx assay that can detect a more comprehensive set of markers, is inexpensive and cost-effective. The test is currently validated on tissue biopsy samples; however, we intend to translate this test to a liquid biopsy platform to monitor treatment resistance in an effective and minimally invasive manner.