Association between Circulating Osteocalcin and Cardiometabolic Risk Factors following a 4-Week Leafy Green Vitamin K-Rich Diet. Epub 2016 Jul 22. The epidermal growth factor receptor (EGFR) is among the most widely studied growth factor receptors due to its ubiquity and pleiotropic signaling effects. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Petrelli F, Borgonovo K, Cabiddu M et al. Schneider-Merck T, Lammerts van Bueren JJ, Berger S et al. Whether hypokalemia induced by cetuximab therapy is related to impaired renal handling or intestinal loss needs to be clarified by further studies. Increasing potassium is required to repair Na/K-ATPase due to the magnesium deficiency. Inhibitors of the epidermal growth factor receptor (EGFR) are increasingly used in the treatment of various entities of malignant tumors. The use of EGFR inhibitor agents is expected to increase in the coming years. Evidence of a common mechanism. Pro-epidermal growth factor (pro-EGF) and magnesium permeable transient receptor potential cation channel (TRPM6 channel, subfamily M, member 6 and TRPM7) were both shown to be involved in transepithelial Mg2+ transport in the distal convoluted tubule [58], which is the main site of active renal Mg2+ reabsorption. It should be pointed out that the two anti-EGFR MAbs cetuximab and panitumumab are commonly employed along with cytotoxic chemotherapy, the latter potentially being able to contribute, directly or through the induction of adverse events such as vomiting and diarrhea, to kidney injury [51]. Correspondence and offprint requests to: Hassan Izzedine; E-mail: Search for other works by this author on: Small-molecule EGFR tyrosine kinase inhibitors for the treatment of cancer, EGF-ERBB signalling: towards the systems level, Biomarkers that currently affect clinical practice: EGFR, ALK, MET, KRAS, EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992, Integration of EGFR inhibitors with radiochemotherapy, Clinical application of epidermal growth factor receptor tyrosine kinase inhibitors against NSCLC, Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway, EGFR signaling promotes TGFβ-dependent renal fibrosis, Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis, EGF receptor deletion in podocytes attenuates diabetic nephropathy, Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial), Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial, West Japan Oncology Group. Vitamin D in Preterm and Full-Term Infants. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. 2020 May 19;10:779. doi: 10.3389/fonc.2020.00779. Selected EGFR tyrosine kinase inhibitors in NSCLC (and other cancers). EGFR, epidermal growth factor receptor; VEGFR, vascular endothelial growth factor receptor; MAbs, monoclonal antibodies; TKIs, tyrosine kinase inhibitors. Thus, the authors postulated that inhibitors of the EGFR cascade may actually be useful for preventing severe renal damage and renal failure [10]. | Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. mechanisms behind these adverse effects and points to an add-on treatment that mighthelptopreventthem. 2016 Dec;21(12):1483-1491. doi: 10.1634/theoncologist.2016-0051. Cetuximab and panitumumab are most effective in combination with chemotherapy, but also show activity as single agents in chemorefractory mCRC [35]. As for afatinib, a 34 and 3% incidence of hypokalemia of all grades and of grade 3/4, respectively, has been reported [51, 75]. All rights reserved. Furthermore, in combination with gemcitabine, erlotinib was approved as a treatment for pancreatic cancer [21]. All conditions Breast Cancer Breast Cancer, Adjuvant Breast Cancer, Metastatic Colorectal Cancer Head and Neck Cancer Non-Small Cell Lung Cancer Pancreatic Cancer Squamous Cell Carcinoma Thyroid Cancer. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). cetuximab (Erbitux™) and panitumumab (Vectibix™)] (Figure 1). Colorectal cancer patients had the highest risk of grade 3/4 hypomagnesemia events among cancer patients: compared with chemotherapy alone, addition of cetuximab increased the risk of grade 3/4 hypomagnesemia with RRs of 7.14 (95% CI 3.13–16.27, P < 0.001) while panitumumab cases were more vulnerable to grade 3/4 hypomagnesemia (RR 18.29, 95% CI 7.29–48.41, P < 0.001) [52]. The major risk factor for the development of hypomagnesemia was the duration of treatment: grade 3 and 4 hypomagnesemia ranging from 6% to 47% in relation to the duration of treatment time <3 months or >6 months, respectively [51, 54]. Response to therapy has been reported for six patients: four of them received treatment with glucocorticoids coupled with discontinuation of anti-EGFR agent, resulting in complete or partial improvement in proteinuria in three and one patients, respectively. Side effects of oral EGFR inhibitors (Gefitinib/ Erlotinib/Afatinib) The adverse drug reactions most commonly reported were rash (possibly itchy) and diarrhea , which in most cases were mild and manageable without intervention. Management of adverse events during treatment of gastrointestinal cancers with epidermal growth factor inhibitors. In addition, there have been several cases of leukocytoclastic vasculitis during treatment with erlotinib [88] or gefitinib [89] and one case report of ANCA-negative pauci-immune crescentic glomerulonephritis during erlotinib [83] therapy. Thus, pathogenic mechanisms of these renal adverse events require more investigation. No obvious higher risk of hyponatremia events related to MAbs was discovered. The epidermal growth factor receptor (EGFR) is implicated in various malignancies. All rights reserved. Overview of the VEGFR and EGFR signaling pathways and drugs targeting signaling proteins and receptors. FDA approved (2007, metastatic breast cancer), Phase II (metastatic gastric, cholangiocarcinoma), Third-generation/mutant-selective EGFR TKIs, Kicked Out Of Bar For Being Too Drunk,
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