Abstract
Colorectal cancer (CRC) is the third prevalent cancer worldwide, the morbidity and mortality of which have been increasing in recent years. As molecular targeting agents, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (McAbs) have significantly increased the progression-free survival (PFS) and overall survival (OS) of metastatic CRC (mCRC) patients. Nevertheless, most patients are eventually resistant to anti-EGFR McAbs. With the intensive study of the mechanism of anti-EGFR drug resistance, a variety of biomarkers and pathways have been found to participate in CRC resistance to anti-EGFR therapy. More and more studies have implicated non-coding RNAs (ncRNAs) primarily including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely involved in tumorigenesis and tumor progression. They function as essential regulators controlling the expression and function of oncogenes. Increasing data have shown ncRNAs affect the resistance of molecular targeted drugs in CRC including anti-EGFR McAbs. In this paper, we have reviewed the advance in mechanisms of ncRNAs in regulating anti-EGFR McAbs therapy resistance in CRC. It provides insight into exploring ncRNAs as new molecular targets and prognostic markers for CRC.
Highlights
Colorectal cancer (CRC) is the third most frequent cancer worldwide
We have focused on current progress in the underlying molecular mechanisms of non-coding RNAs (ncRNAs) in regulating the resistance to anti-epidermal growth factor receptor (EGFR) therapy in CRC
EGFR signaling pathway has been confirmed to be aberrantly activated in multiple malignant tumors, which is associated with tumor progression and prognosis
Summary
CRC is the third most frequent cancer worldwide. Global cancer statistics in 2020 has shown there are about 1.932 million new cases and 935,000 deaths of CRC worldwide, accounting for 10.0% of the total new cases of cancer and 9.4% of the total cancer-related deaths, respectively [1]. NcRNAs in CRC Drug Resistance mCRC patients carrying wild-type RAS and BRAF [4]. Abnormal expression and activation of any signal molecules mentioned above may lead to primary (de novo) or acquired (secondary) resistance to anti-EGFR therapy in mCRC [5]. Abnormal EGFR gene copy number, protein expression of EGFR ligands, HER2 and MET gene amplifications, and activation of EGFR downstream cascade signaling pathways [including the mutations of RAS/BRAF/PIK3CA, the loss of PTEN, STAT3 phosphorylation, and epithelial-mesenchymal transition (EMT)], have been demonstrated to be associated with the primary resistance to anti-EGFR therapy in CRC [5, 7, 8]. We have focused on current progress in the underlying molecular mechanisms of ncRNAs in regulating the resistance to anti-EGFR therapy in CRC.
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