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

精准医学方法将可用的治疗方法与患者的生物学结合起来，以便为特定疾病提供最合适的治疗方法。在结肠直肠癌中，治疗通常针对表皮生长因子受体，这是一种存在于细胞表面的生物标志物。然而，如果患者的肿瘤中含有KRAS、NRAS和BRAF基因的某些突变，EGFR治疗将无效。因此，确定结直肠癌的肿瘤突变状态对临床医生提供最佳治疗方案至关重要。这使患者能够更快地获得最相关的治疗，从而改善了患者的治疗效果，避免了不必要的副作用，并防止患者接受昂贵的不成功的治疗。然而，在大多数情况下，最初有资格接受抗egfr治疗的患者会对这些治疗产生获得性耐药性。抗egfr耐药性可由上述基因的肿瘤进化突变引起。因此，持续监测这些患者的突变状态至关重要。目前，治疗一直持续到患者出现疾病进展迹象，这意味着患者在获得替代治疗方面面临延迟，这可能会影响患者的预后，因为继续治疗可能会产生令人不快的副作用，并导致昂贵的治疗无效。因此，在整个疾病进展过程中有效监测患者的突变状态至关重要。目前KRAS、NRAS和BRAF在诊断和整个疾病过程中检测的金标准是通过组织活检，这对患者来说是侵入性的和不愉快的。在最初诊断之外，并不总是能够获得额外的组织活检，这对持续监测患者构成了挑战。我们的目标是开发一种创新的基于液体活检的检测方法来确定和监测患者的RASRAF基因突变状态。BioClavis开发了一种基于TempO-Dx分析的更有效的检测方法，可以检测更全面的标记物，价格低廉且具有成本效益。该测试目前在组织活检样本上进行验证；然而，我们打算将这种测试转化为液体活检平台，以有效和微创的方式监测治疗耐药性。

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.