What are the molecular mechanisms underlying the inhibitory effect of cetuximab on cancer cells?
Best insight from top research papers
Cetuximab inhibits cancer cells through multiple molecular mechanisms. It downregulates the alpha subunit of hypoxia-inducible factor-1 (HIF-1α) by inhibiting EGF receptor downstream cell signaling, leading to the inhibition of glycolysis and mitochondrial respiration . Cetuximab also enhances radiosensitivity in esophageal squamous cell carcinoma (ESCC) by promoting G2/M cell cycle arrest, reducing DNA double-strand break repair, and inhibiting the EGFR and downstream ERK pathways . In addition, cetuximab resistance mediated by hepatocyte growth factor (HGF)-dependent mesenchymal-epithelial transition factor (MET) activation can be overcome by blocking HGF/MET signaling . Furthermore, ERBB2 signaling activation is another mechanism for cetuximab resistance, and simultaneous inhibition of ERBB2 and EGFR has shown promise in overcoming resistance . These findings provide insights into the molecular mechanisms underlying the inhibitory effect of cetuximab on cancer cells.
Answers from top 4 papers
More filters
| Papers (4) | Insight |
|---|---|
01 Jan 2023 | The provided paper does not discuss the molecular mechanisms underlying the inhibitory effect of cetuximab on cancer cells. |
03 Apr 2023 | The paper provides mechanistic insights into the inhibitory effect of cetuximab on cancer cells by showing that cetuximab downregulates lactate dehydrogenase A (LDH-A) and inhibits glycolysis in cetuximab-sensitive head and neck squamous cell carcinoma (HNSCC) cells in an HIF-1α downregulation-dependent manner. |
03 Apr 2023 | The paper provides mechanistic insights into the inhibitory effect of cetuximab on cancer cells by showing that cetuximab downregulates lactate dehydrogenase A (LDH-A) and inhibits glycolysis in cetuximab-sensitive head and neck squamous cell carcinoma (HNSCC) cells in an HIF-1α downregulation-dependent manner. |
| The molecular mechanisms underlying the inhibitory effect of cetuximab on cancer cells include the suppression of phosphorylation of EGFR and downstream ERK pathways. |
Related Questions
What is the mechanism behind Cetuximab?5 answersCetuximab, an EGFR-targeted therapy, exerts its effects through various mechanisms. In colorectal cancer, it has been found that PLCγ1 plays a crucial role in predicting responses to cetuximab. In head and neck squamous cell carcinoma (HNSCC), cetuximab's efficacy is associated with adverse events like skin rash and acquired resistance linked to microenvironment plasticity. Additionally, prolonged cetuximab treatment in HNSCC cell lines leads to decreased cell motility, G1 phase cell arrest, and autophagy, indicating its impact on cell cycle progression and migration. Moreover, in metastatic colorectal cancer, cetuximab induces immunogenic cell death (ICD) when combined with chemotherapy, enhancing antitumor responses through ER stress and increased phagocytosis by dendritic cells. These diverse mechanisms shed light on cetuximab's multifaceted actions in different cancer types.
What are the effects of blocking or inhibiting the SCF-c-kit signaling pathway in different cancer?5 answersBlocking or inhibiting the SCF-c-kit signaling pathway has been shown to have different effects in various types of cancer. In gastrointestinal stromal tumor (GIST), a SCF-emtansine drug conjugate (SCF-DM1) was effective in inhibiting imatinib-sensitive and -resistant GIST cells, inducing apoptosis and cell cycle arrest. In erythroleukemia, a c-kit antagonist human antibody (NN2101) completely blocked SCF-mediated phosphorylation of c-kit and inhibited cell proliferation. However, in non-small cell lung cancer (NSCLC) and prostate cancer, the inhibition of the SCF/c-kit pathway did not significantly affect cell survival or radioresponse, except in cases of strong overexpression of SCF. In neurogenic bladder, inhibition of the SCF/c-kit pathway impaired SCF-induced attenuation of interstitial cells of Cajal (ICC) damage. In mucinous colorectal adenocarcinoma (MCA), hypo-activation of SCF/c-kit signaling resulted in crippled mucus secretion, while activation of the pathway promoted mucus secretion through the activation of PKCδ-MARCKS.
What are the mechanisms by which molecular targeting therapies affect the apoptotic pathways in cancer cells?5 answersMolecular targeting therapies affect the apoptotic pathways in cancer cells through various mechanisms. These therapies aim to induce apoptosis, which is the programmed cell death process. They target anti-apoptotic molecules and enhance pro-apoptotic molecules to overcome resistance to conventional cancer treatments. The therapies can modulate the expression of apoptotic genes, regulate the activity of caspase proteases, and affect the balance between pro-apoptotic and anti-apoptotic proteins. They can also target specific pathways involved in apoptosis, such as the death receptor pathway, the mitochondrial pathway, and the endoplasmic reticulum stress pathway. Additionally, the therapies can disrupt signaling pathways, such as the TNFα/NF-κB pathway, that regulate apoptosis. The development of predictive biomarkers and rational combination strategies is crucial for the successful development of these therapies.
What is the precise molecular mechanism by which DNA methylation inhibitors, such as 5-aza-2-dC, antagonize the cancer methylation program?5 answersDNA methylation inhibitors, such as 5-aza-2-dC, antagonize the cancer methylation program by inhibiting DNA methyltransferases (DNMTs), leading to passive demethylation of 5'methylcytosines (5mC) in rapidly dividing tissues. This results in the reactivation of silenced tumor-suppressor genes and cell death. The precise molecular mechanism of action involves the inhibition of DNMTs, specifically DNMT1, which is responsible for hypermethylation of CpG regions and silencing of tumor-suppressor genes. The inhibitors cause hypomethylation of genomic DNA, including repetitive DNA elements, and show dose-dependent effects on DNA methylation. However, the exact mechanism by which these inhibitors interact with DNMTs and disrupt the methylation program is still being studied. Further research is needed to fully understand the molecular details of how DNA methylation inhibitors antagonize the cancer methylation program.
Why immune-checkpoint inhibitors are less effective in colorectal cancer patients than other cancer types?3 answersImmune checkpoint inhibitors (ICIs) are less effective in colorectal cancer (CRC) patients compared to other cancer types. The reason for this is not well understood, but several factors have been identified. Somatic mutations, particularly missense mutations in the axonemal dynein heavy chain gene 7 (DNAH7), play an important role in CRC. Patients with DNAH7 mutations have been found to benefit more from ICIs, suggesting that these mutations may impact the clinical efficacy of ICIs in CRC. Additionally, the tumor immune microenvironment in CRC patients with DNAH7 mutations is different, with higher ESTIMATE scores, immune scores, and matrix scores, indicating a more favorable immune response. Furthermore, the majority of CRC patients are microsatellite stable (MSS), which has been associated with immunorefractory disease. However, sequential treatment with ICIs followed by chemotherapy has shown promise in enhancing cytotoxic effects in MSS mCRC patients. Overall, further research is needed to fully understand the mechanisms underlying the reduced effectiveness of ICIs in CRC patients.
Is cetuximab chemotherapy or immunotherapy?5 answers