Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer

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.

The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells

“…However, until recently precision medicine which incorporates specific therapeutic agents which correlates with specific tumor characteristics that lead to abnormal expression and defect in biological pathways have gained much interest in the clinical trial setting as well as development of drugs for CRC [ 10 ]. The molecular targets and clinical trials of CRC include targeting the EGF/EGFR, VEGF-VEGF Receptor (VEGFR), MAPK-RAS/FAR/MEK/ERK and PI3K-mTOR pathways via the usage of anti-EGFR and anti-angiogenic monoclonal antibodies, tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI) [ 11 , 12 , 13 , 14 ].…”

Combinatorial Immunotherapies for Metastatic Colorectal Cancer

“…The anti-EGFR monoclonal antibodies cetuximab and panitumumab are active by themselves, resulting in a survival benefit with adequate selection of patients with left-sided tumours with a RAS wild-type status [ 70 ]. Other targeted therapies that were developed for a specific subgroup of patients include treatment with trastuzumab/pertuzumab for HER2+ mCRCs [ 71 ], and the combination of encorafenib (BRAF inhibitor) and cetuximab—which was demonstrated to be efficacious and approved by regulatory agencies for BRAF V600E -mutant mCRC [ 72 ]. Additional trials investigating regorafenib (a multikinase inhibitor) and trifluridine/piperacil (a nucleoside analogue) have shown modest improvement compared to best supportive care [ 73 , 74 ].…”

Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

“…Colorectal cancer (CRC) is the fourth most common tumor and it stands at the second place for cancer death worldwide ( 1 ). Almost 20% of CRC patients are diagnosed at an advanced stage and approximately a further 20% develop metastases later in life ( 2 ). Nowadays, it is well known that tumor-driven angiogenesis plays a crucial role in CRC growth and metastatic spread ( 3 – 15 ).…”