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- W2967718330 abstract "Objective: To evaluate the efficacy and treatment rationale of Hürthle cell carcinoma (HCC) following a patient with progressive and metastatic HCC. HCC was recently shown to harbor a distinct genetic make-up and the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kiase (PI3K)/AKT signaling pathways are potential targets for anti-cancer agents in the management of recurrent HCC. The presence or absence of gene variants can give a rationale for targeted therapies that could be made available in the context of drug repurposing trials. Methods: Treatment included everolimus, sorafenib, nintedanib, lenvatinib, and panitumumab. Whole genome sequencing (WGS) of metastatic tumor material obtained before administration of the last drug, was performed. We subsequently evaluated the rationale and efficacy of panitumumab in thyroid cancer and control cell lines after epidermal growth factor (EGF) stimulation and treatment with panitumumab using immunofluorescent Western blot analysis. EGF receptor (EGFR) quantification was performed using flow cytometry. Results: WGS revealed a near-homozygous genome (NHG) and a somatic homozygous TSC1 variant, that was absent in the primary tumor. In the absence of RAS variants, panitumumab showed no real-life efficacy. This might be explained by high constitutive AKT signaling in the two thyroid cancer cell lines with NHG, with panitumumab only being a potent inhibitor of pEGFR in all cancer cell lines tested. Conclusions: In progressive HCC, several treatment options outside or inside clinical trials are available. WGS of metastatic tumors might direct the timing of therapy. Unlike other cancers, the absence of RAS variants seems to provide insufficient justification of single-agent panitumumab administration in HCC cases harboring a near-homozygous genome." @default.
- W2967718330 created "2019-08-22" @default.
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- W2967718330 date "2019-08-15" @default.
- W2967718330 modified "2023-09-28" @default.
- W2967718330 title "Targeted Treatment Options of Recurrent Radioactive Iodine Refractory Hürthle Cell Cancer" @default.
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- W2967718330 doi "https://doi.org/10.3390/cancers11081185" @default.
- W2967718330 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6721552" @default.
- W2967718330 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31443247" @default.
- W2967718330 hasPublicationYear "2019" @default.
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