Colorectal cancers (CRC) belonging to the consensus molecular subtype 2 (CMS2) have the highest incidence rate, affect mainly the distal colon and rectum, and are characterized by marked Wnt/β-catenin/Transcription Factor 7-Like 2 (TCF7L2) pathway activation and also by activation of epidermal growth factor receptor (EGFR) signalling.
Importantly, this work demonstrated that the acetylated cycloartane glycosides <b>1</b> and <b>4</b> might preferentially inhibit cell growth in the CRC cell model resistant to epidermal growth factor receptor (EGFR) inhibitors.
KEY POINTS: To the authors' knowledge, this is the first report of <i>EGFR</i>-<i>SEPT14</i> fusion in colorectal cancer.The patient achieved a partial response after treatment with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib.This report expands the list of gene fusions in colorectal cancer and highlights new targets for the therapeutic intervention.
For example, agents inhibiting the epidermal growth factor receptor (EGFR) benefit many colorectal cancer (CRC) patients, with the general exception of those whose tumor includes a <i>KRAS</i> mutation.
Human epidermal growth factor receptor 2 (HER2) activation is present in approximately 5% of CRC and has acquired resistance to epidermal growth factor receptor (EGFR)-targeted therapy.
Particularly relevant in CRC are the activating mutations in the oncogene PIK3CA that frequently occur in concomitancy with KRAS and BRAF mutations and that lead to deregulation of the major signalling pathways PI3K and MAPK, downstream of EGFR.
This study, therefore, identified five candidate microRNAs, two hub genes (CTNNB1 and epidermal growth factor receptor), and seven significant target genes associated with colorectal cancer.
We proved that some miR-425-5p targeted genes are involved in EGFR tyrosine kinase inhibitor resistance pathway, suggesting that therapies based on miR-425-5p may have strong potential in targeting KRAS-driven CRC.
The targeting of activated epidermal growth factor receptor (EGFR) with therapeutic anti-EGFR monoclonal antibodies (mAbs) such as cetuximab and panitumumab has been used as an effective strategy in the treatment of colorectal cancer (CRC).
Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer.
In this review, we provide deep insights into the development of EGFR-targeting nanomedicines and discuss various types of nanoscale DDSs (e.g., organic and inorganic nanoparticles) for targeting of the EGFR-positive solid tumors such as CRC.
Cetuximab (CTX), a monoclonal antibody against epidermal growth factor receptor, is being widely used for colorectal cancer (CRC) with wild-type (WT) KRAS.
Our results show that genetic and pharmacologic interference with PDEδ specifically inhibits proliferation and survival of CRC cell lines harboring oncogenic KRas mutations whereas isogenic cell lines in which the KRas oncogene has been removed, or cell lines with oncogenic BRaf mutations or EGFR overexpression are not dependent on PDEδ.
miR-145-5p restrained cell growth, invasion, migration and tumorigenesis via modulating RHBDD1 in colorectal cancer via the EGFR-associated signaling pathway.
Signal transducer and activator of transcription 3 (STAT3) and its mediated signal transduction pathway play an important role in the occurrence, development and metastasis of CRC, and are related to the development of EGFR-TKI resistance in CRC.
The US Food and Drug Administration approved a liquid biopsy test for EGFR-activating mutations in patients with non-small-cell lung cancer as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFRT790M in non-small-cell lung cancer. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAF V600E/V600K in melanoma.
Broad-spectrum receptor tyrosine kinase inhibitors overcome <i>de novo</i> and acquired modes of resistance to EGFR-targeted therapies in colorectal cancer.
The optimal management of hypomagnesemia (hMg) induced by epidermal growth factor receptor inhibitors (egfris) for advanced colorectal cancer is unclear.
According to Dr. Wells A. Messersmith, targeted therapies (ie, VEGFR, EGFR, multitargeted tyrosine kinase inhibitors) play an important role in CRC management, but none of them have been successful in the adjuvant setting (although checkpoint inhibition is now being tested in MSI-high stage III CRC).
To the best of our knowledge, this is the first study to examine the combination of CC3/LC3B and p-MLKL expression in clinical CRC samples and to correlate these expression data with clinicopathological parameters and EGFR and p53 status.
SIGNIFICANCE: Menin acts as a calcium-responsive regulator of SKP2 expression, and small molecule EGFR inhibitors, which induce calcium release, synergize with Menin inhibition to reduce SKP2 expression and suppress colorectal cancer.