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

将 TempO-Dx Expanded RASRAF 测试标记物转化到液体活检平台上，用于监测结直肠癌的治疗耐药性

• 批准号: 10027086
• 金额: $ 30.21万
• 依托单位: BIOCLAVIS LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10027086
• 关键词: Translation; TempO; Dx; Expanded; RASRAF

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.

精准医学方法将现有疗法与患者的生物学相结合，以便为特定疾病病例提供最合适的治疗方法。在结直肠癌中，治疗通常以EGFR为靶点，EGFR是细胞表面的生物标志物。然而，如果患者的肿瘤在基因KRAS、NRAS和BRAF中存在某些突变，则EGFR治疗将无效。因此，确定结直肠癌中的肿瘤突变状态对于建议临床医生最佳治疗方案至关重要。这通过使患者更快地获得最相关的治疗来改善患者的预后，避免不必要的副作用，并防止患者接受昂贵的不成功治疗。然而，已知最初符合抗EGFR治疗条件的患者在大多数情况下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中的肿瘤演变突变引起。因此，持续监测这些患者的突变状态至关重要。目前，治疗一直持续到病人出现疾病进展的迹象，这意味着病人在获得替代治疗方面面临延误，这可能会影响病人的预后，因为治疗继续下去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，在病人疾病进展的整个过程中，有效监测病人的突变状态是必不可少的。目前诊断时和整个疾病过程中KRAS、NRAS和BRAF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。除了最初的诊断之外，获得额外的组织活检并不总是可能的，这对患者的持续监测构成了挑战。我们的目标是开发一种创新的基于液体活检的测试，以确定和监测患者的RASRAF基因突变状态。BioClavis开发了一种基于TempO-Dx检测的更有效的检测方法，可以检测更全面的标志物，价格低廉，具有成本效益。该测试目前在组织活检样本上得到验证;然而，我们打算将该测试转化为液体活检平台，以有效和微创的方式监测治疗阻力。