Abstract
Background: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. Methods: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. Results: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-β, which require further research. Conclusion: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients.
Highlights
Colorectal cancer (CRC) is the second most common tumor worldwide and the second leading cancer (CRC) is the second20%mostof common tumor worldwide and the second cause ofColorectal cancer death [1]
Several molecular biomarkers have been identified for the personalized treatment of metastatic CRC (mCRC) patients and extensive efforts have been made to improve tailored therapy
rat sarcoma (RAS) mutational status determination remains mandatory before starting anti-epidermal growth factor receptor (EGFR) treatment with panitumumab and cetuximab, and the new approach of rechallenge based on RAS/BRAF status by liquid biopsy is becoming more fascinating [13,14,15,16,17,18,19,20,21,22,23,24,25]
Summary
Colorectal cancer (CRC) is the second most common tumor worldwide and the second leading cancer (CRC). Robust research demonstrated that metastatic CRC (mCRC) is not one therapy. Robust research demonstrated that metastatic CRC (mCRC) is not one single entity, but rather a complex disease characterized by significant molecular heterogeneity [2]. In the era of precision medicine, it is crucial to identify predictive biomarkers to tailor treatment and to. In the era of precision medicine, it is crucial to identify predictive biomarkers to tailor treatment and identify the patients who are more likely to respond to specific therapeutic agents. Several biomarkers related pathways have been investigated potential targets, and molecularand biomarkers and related pathways have beenasinvestigated as potential targets, and a wide variety of drugs been including monoclonal antibodies (mAbs), small (mAbs), molecule a widehave variety of developed, drugs have been developed, including monoclonal antibodies tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICI).
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