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Molecular Approaches to Metastatic Colorectal Cancer: Better Diagnosis - Better Treatment?

ABSTRACT: Molecular diagnostics of metastatic colorectal cancer (mCRC) are coming of age. Whereas for many years RAS mutations were the only relevant molecular alterations examined in mCRC, nowadays the BRAF, HER2, and microsatellite instability status of a given tumor is gaining importance, since it has not only prognostic relevance but opens new avenues for therapeutic approaches. This review summarizes the recent advances in molecular approaches to mCRC and their therapeutic consequences and discusses novel approaches for molecular diagnostics in mCRC.

SUBMITTER: Seufferlein T

PROVIDER: S-EPMC6738174 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Molecular Approaches to Metastatic Colorectal Cancer: Better Diagnosis - Better Treatment?

Seufferlein Thomas T Simões Carolina C Kude Fernando F Ettrich Thomas J TJ

Visceral medicine 20190711 4

Molecular diagnostics of metastatic colorectal cancer (mCRC) are coming of age. Whereas for many years RAS mutations were the only relevant molecular alterations examined in mCRC, nowadays the BRAF, HER2, and microsatellite instability status of a given tumor is gaining importance, since it has not only prognostic relevance but opens new avenues for therapeutic approaches. This review summarizes the recent advances in molecular approaches to mCRC and their therapeutic consequences and discusses ...[more]

PMID: 31602389

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Project description:BackgroundRAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice.Patients and methodsRAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients.ResultsAnalysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment.ConclusionThe high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.

Dataset Information

Molecular Approaches to Metastatic Colorectal Cancer: Better Diagnosis - Better Treatment?

Publications

Molecular Approaches to Metastatic Colorectal Cancer: Better Diagnosis - Better Treatment?

Similar Datasets

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