Next Article in Journal
Clinical Relevance of Collagen Protein Degradation Markers C3M and C4M in the Serum of Breast Cancer Patients Treated with Neoadjuvant Therapy in the GeparQuinto Trial
Next Article in Special Issue
Development, Implementation and Assessment of Molecular Diagnostics by Next Generation Sequencing in Personalized Treatment of Cancer: Experience of a Public Reference Healthcare Hospital
Previous Article in Journal
Hyperthermia Treatment Planning Including Convective Flow in Cerebrospinal Fluid for Brain Tumour Hyperthermia Treatment Using a Novel Dedicated Paediatric Brain Applicator
Previous Article in Special Issue
Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle

Targeted Treatment Options of Recurrent Radioactive Iodine Refractory Hürthle Cell Cancer

1
Department of Medical Oncolosgy, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2
Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
3
Hartwig Medical Foundation, 1098 XH Amsterdam, The Netherlands
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(8), 1185; https://doi.org/10.3390/cancers11081185
Received: 30 July 2019 / Accepted: 13 August 2019 / Published: 15 August 2019
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
  |  
PDF [11096 KB, uploaded 15 August 2019]
  |     |  

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. View Full-Text
Keywords: Hürthle cell carcinoma; thyroid neoplasm; near-homozygous genome; targeted therapy; panitumumab; humans; cell line; tumor; cell signaling; epidermal growth factor receptor; AKT Hürthle cell carcinoma; thyroid neoplasm; near-homozygous genome; targeted therapy; panitumumab; humans; cell line; tumor; cell signaling; epidermal growth factor receptor; AKT
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Aydemirli, M.D.; Corver, W.; Beuk, R.; Roepman, P.; Solleveld-Westerink, N.; van Wezel, T.; Kapiteijn, E.; Morreau, H. Targeted Treatment Options of Recurrent Radioactive Iodine Refractory Hürthle Cell Cancer. Cancers 2019, 11, 1185.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top