Clin Osteol 2024; 29(3): 80-83
The EGFR signaling pathway is involved in the regulation of cellular functions of osteoclasts and osteoblasts. Suppression of signaling in this pathway by administration of EGFR-TKIs has been used as an option for anticancer therapy in NSCLC patients with activating mutations of the EGFR gene. We describe the case of an NSCLC patient treated with afacitinib in whom we observed a significant suppression of bone remodeling accompanied by an increase in BMD, which was further potentiated by downstream administration of denosumab. The effect of EGFR-TKI inhibition on bone metabolism has not been sufficiently studied. In vitro data show that EGFR inhibition leads to attenuation of osteoblast and osteoclast activity. Further research is also desirable in view of important overlaps into clinical practice (bone metastases, Skeletal-Related Events, OsteoNecrosis of the Jaw).Case reports
- 1 Osteocentrum Affidea Praha, s. r. o.
- 2 LF UK v Hradci Králové
- 3 Centrum biomedicínského výzkumu FN Hradec Králové
- 4 Ústav klinické biochemie a diagnostiky FN Hradec Králové
Signální dráha receptoru pro epidermální růstový faktor (EGFR) se podílí na regulaci buněčných funkcí osteoklastů i osteoblastů. Útlum signalizace v této dráze aplikací inhibitorů tyrozinkinázy (EGFR-TKI) je využíván jako varianta protinádorové terapie u pacientů s nemalobuněčným karcinomem plic (NSCLC) s aktivačními mutacemi genu EGFR. Popisujeme případ pacientky s NSCLC léčené afacitinibem, u níž jsme pozorovali významnou supresi kostní remodelace doprovázenou vzestupem BMD, která byla dále potencována navazující aplikací denosumabu. Vliv inhibice EGFR-TKI na kostní metabolizmus není dostatečně prostudován. In vitro data ukazují, že inhibice EGFR vede k útlumu aktivity osteoblastů i osteoklastů. Další výzkum je žádoucí i s ohledem na významné přesahy do klinické praxe - kostní metastázy, nádorová postižení skeletu (SRE), osteonekróza čelisti (ONJ).
Keywords: Epidermal Growth Factor Receptor (EGFR); Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI); afatinib; Bone Mineral Density (BMD); C-terminal Telopep-tide (CTX); Procollagen type 1 N-terminal Propeptide (P1NP)
Published: December 11, 2024 Show citation
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Jan R, Fabrik I, Soukup O, Palička V. The EGFR signaling pathway is involved in the regulation of cellular functions of osteoclasts and osteoblasts. Suppression of signaling in this pathway by administration of EGFR-TKIs has been used as an option for anticancer therapy in NSCLC patients with activating mutations of the EGFR gene. We describe the case of an NSCLC patient treated with afacitinib in whom we observed a significant suppression of bone remodeling accompanied by an increase in BMD, which was further potentiated by downstream administration of denosumab. The effect of EGFR-TKI inhibition on bone metabolism has not been sufficiently studied. In vitro data show that EGFR inhibition leads to attenuation of osteoblast and osteoclast activity. Further research is also desirable in view of important overlaps into clinical practice (bone metastases, Skeletal-Related Events, OsteoNecrosis of the Jaw). Clinical Osteology. 2024;29(3):80-83.
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