Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2018

01-10-2018 | Original Article

Expression of vascular endothelial growth factor receptor 2 and clinical response to lenvatinib in patients with anaplastic thyroid cancer

Authors: Haruhiko Yamazaki, Tomoyuki Yokose, Hiroyuki Hayashi, Hiroyuki Iwasaki, Sachie Osanai, Nobuyasu Suganuma, Hirotaka Nakayama, Katsuhiko Masudo, Yasushi Rino, Munetaka Masuda

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2018

Login to get access

Abstract

Purpose

Angiogenesis plays a crucial role in the development, growth, and metastasis of carcinomas, and studies have reported conflicting evidence regarding the VEGFR expression in anaplastic thyroid cancer. We investigated the expression of VEGFR2 in patients with anaplastic thyroid cancer (ATC) and analyzed the clinical response to the VEGFR inhibitor lenvatinib.

Methods

This cross-sectional study included primary tumor samples obtained from 12 patients with ATC, including 5 males and 7 females (age range 63–89 years) who underwent surgery or core needle biopsy for a thyroid tumor in the Department of Breast and Endocrine Surgery at Kanagawa Cancer Center in Kanagawa, Japan. VEGFR2 protein expression in the ATC samples was analyzed by immunohistochemistry in all patients, and the therapeutic effect of lenvatinib was evaluated in seven patients who underwent tissue biopsy and lesion evaluation.

Results

VEGFR expression was not detected in any of the samples from the 12 patients. Four of the 12 patients treated with lenvatinib had partial response, the three patients achieved stable disease, and the five patients were not examined.

Conclusions

There was no correlation between the expression of VEGFR2 in tumor tissue and the clinical response to lenvatinib among patients with ATC. Further studies are necessary to elucidate the mechanism underlying the response to lenvatinib.
Literature
1.
2.
Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25CrossRefPubMed
3.
Klein M, Catargi B (2007) VEGF in physiological process and thyroid disease. Ann Endocrinol (Paris) 68:438–448CrossRef
4.
Petrova TV, Makinen T, Alitalo K (1999) Signaling via vascular endothelial growth factor receptors. Exp Cell Res 253:117–130CrossRefPubMed
5.
Fournier E, Birnbaum D, Borg JP (1997) Receptors for factors of the VEGF (Vascular Endothelial Growth Family). Bull Cancer 84:397–405PubMed
6.
Parast CV, Mroczkowski B, Pinko C, Misialek S, Khambatta G, Appelt K (1998) Characterization and kinetic mechanism of catalytic domain of human vascular endothelial growth factor receptor-2 tyrosine kinase (VEGFR2 TK), a key enzyme in angiogenesis. Biochemistry 37:16788–16801CrossRefPubMed
7.
Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, Sawada T, Sowa M (1996) Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 77:858–863CrossRefPubMed
8.
Inoue K, Ozeki Y, Suganuma T, Sugiura Y, Tanaka S (1997) Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma. Association with angiogenesis and tumor progression. Cancer 79:206–213CrossRefPubMed
9.
Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P, Gatti C, Suzuki H, Tominaga T (1997) Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst 89:139–147CrossRefPubMed
10.
Yamamoto S, Konishi I, Mandai M, Kuroda H, Komatsu T, Nanbu K, Sakahara H, Mori T (1997) Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasms: correlation with clinicopathology and patient survival, and analysis of serum VEGF levels. Br J Cancer 76:1221–1227CrossRefPubMedPubMedCentral
11.
Salven P, Teerenhovi L, Joensuu H (1997) A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin’s lymphoma. Blood 90:3167–3172PubMed
12.
Erdem H, Gündogdu C, Sipal S (2011) Correlation of E-cadherin, VEGF, COX-2 expression to prognostic parameters in papillary thyroid carcinoma. Exp Mol Pathol 90:312–317CrossRefPubMed
13.
Yu XM, Lo CY, Lam AK, Leung P, Luk JM (2008) Serum vascular endothelial growth factor C correlates with lymph node metastases and high-risk tumor profiles in papillary thyroid carcinoma. Ann Surg 247:483–489CrossRefPubMed
14.
Yu XM, Lo CY, Lam AK, Lang BH, Leung P, Luk JM (2008) The potential clinical relevance of serum vascular endothelial growth factor (VEGF) and VEGF-C in recurrent papillary thyroid carcinoma. Surgery 144:934–940 (discussion 940–941)CrossRefPubMed
15.
Sugitani I, Miyauchi A, Sugino K, Okamoto T, Yoshida A, Suzuki S (2012) Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. World J Surg 36:1247–1254CrossRefPubMed
16.
Tiedje V, Stuschke M, Weber F, Dralle H, Moss L, Führer D (2018) Anaplastic thyroid carcinoma: review of treatment protocols. Endocr Relat Cancer Mar 25(3):R153–R161CrossRef
17.
Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A (2001) Prognostic factors and therapeutic strategy for anaplastic carcinoma of the thyroid. World J Surg 25:617–622CrossRefPubMed
18.
Fourati A, El Amine O, Ben Ayoub W, Cherni I, Goucha A, El May MV, Gamoudi A, El May A (2017) Expression profile of biomarkers altered in papillary and anaplastic thyroid carcinoma: contribution of Tunisian patients. Bull Cancer 104:433–441CrossRefPubMed
19.
Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI (2015) Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372:621–630CrossRefPubMed
20.
Takahashi S, Tahara M, Kiyota N, Yamazaki T, Chayahara N, Nakano K, Inagaki R, Toda K, Enokida T, Minami H, Imamura Y, Sasaki T, Suzuki T, Fujino K, Dutcus C (2014) Phase II study of lenvatinib (LEN), a multi-targeted tyrosine kinase inhibitor, in patients (PTS) with all histologic subtypes of advanced thyroid cancer (differentiated, medullary and anaplastic). Ann Oncol 25(Suppl 4):iv340–iv356
21.
Viglietto G, Maglione D, Rambaldi M, Cerutti J, Romano A, Trapasso F, Fedele M, Ippolito P, Chiappetta G, Botti G (1995) Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines. Oncogene 11:1569–1579PubMed
22.
Hung CJ, Ginzinger DG, Zarnegar R, Kanauchi H, Wong MG, Kebebew E, Clark OH, Duh QY (2003) Expression of vascular endothelial growth factor-C in benign and malignant thyroid tumors. J Clin Endocrinol Metab 88:3694–3699CrossRefPubMed
23.
Huang SM, Lee JC, Wu TJ, Chow NH (2001) Clinical relevance of vascular endothelial growth factor for thyroid neoplasms. World J Surg 25:302–306CrossRefPubMed
24.
de Araujo-Filho VJ, Alves VA, de Castro IV, Lourenço SV, Cernea CR, Brandão LG, Ferraz AR (2009) Vascular endothelial growth factor expression in invasive papillary thyroid carcinoma. Thyroid 19:1233–1237CrossRefPubMed
25.
Wiseman SM, Griffith OL, Deen S, Rajput A, Masoudi H, Gilks B, Goldstein L, Gown A, Jones SJ (2007) Identification of molecular markers altered during transformation of differentiated into anaplastic thyroid carcinoma. Arch Surg 142:717–727 (discussion 727–729)CrossRefPubMed
26.
Pinto MP, Sotomayor P, Carrasco-Avino G, Corvalan AH, Owen GI (2016) Escaping antiangiogenic therapy: strategies employed by cancer cells. Int J Mol Sci 17:E1489CrossRefPubMed
27.
Yamamoto Y, Matsui J, Matsushima T, Obaishi H, Miyazaki K, Nakamura K, Tohyama O, Semba T, Yamaguchi A, Hoshi SS, Mimura F, Haneda T, Fukuda Y, Kamata JI, Takahashi K, Matsukura M, Wakabayashi T, Asada M, Nomoto KI, Watanabe T, Dezso Z, Yoshimatsu K, Funahashi Y, Tsuruoka A (2014) Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc Cell 6:18CrossRefPubMedPubMedCentral
28.
Okamoto K, Ikemori-Kawada M, Jestel A, von König K, Funahashi Y, Matsushima T, Tsuruoka A, Inoue A, Matsui J (2014) Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization. ACS Med Chem Lett 6:89–94CrossRefPubMedPubMedCentral
29.
St Bernard R, Zheng L, Liu W, Winer D, Asa SL, Ezzat S (2005) Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology 146:1145–1153CrossRefPubMed
30.
Turkington RC, Longley DB, Allen WL, Stevenson L, McLaughlin K, Dunne PD, Blayney JK, Salto-Tellez M, Van Schaeybroeck S, Johnston PG (2014) Fibroblast growth factor receptor 4 (FGFR4): a targetable regulator of drug resistance in colorectal cancer. Cell Death Dis 5:e1046CrossRefPubMedPubMedCentral
31.
Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe’er J, Trent JM, Meltzer PS, Hendrix MJ (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752CrossRefPubMedPubMedCentral
32.
Seftor RE, Hess AR, Seftor EA, Kirschmann DA, Hardy KM, Margaryan NV, Hendrix MJ (2012) Tumor cell vasculogenic mimicry: from controversy to therapeutic promise. Am J Pathol 181:1115–1125CrossRefPubMedPubMedCentral
Metadata
Title
Expression of vascular endothelial growth factor receptor 2 and clinical response to lenvatinib in patients with anaplastic thyroid cancer
Authors
Haruhiko Yamazaki
Tomoyuki Yokose
Hiroyuki Hayashi
Hiroyuki Iwasaki
Sachie Osanai
Nobuyasu Suganuma
Hirotaka Nakayama
Katsuhiko Masudo
Yasushi Rino
Munetaka Masuda
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3657-x

Other articles of this Issue 4/2018

Cancer Chemotherapy and Pharmacology 4/2018 Go to the issue

Original Article

Phase II trial of capecitabine plus oxaliplatin (CAPOX) as perioperative therapy for locally advanced rectal cancer

Original Article

Randomized controlled clinical trial of polyethylene glycol recombinant human granulocyte colony-stimulating factor in the treatment of neutropenia after chemotherapy for breast cancer

Original Article

Lipid profiling of pre-treatment plasma reveals biomarker candidates associated with response rates and hand–foot skin reactions in sorafenib-treated patients

Clinical Trial Report

A phase I trial of topotecan plus tivantinib in patients with advanced solid tumors

Original Article

Identification and preclinical characterization of a novel and potent poly (ADP-ribose) polymerase (PARP) inhibitor ZYTP1

Original Article

Nab-paclitaxel plus S-1 as first-line followed by S-1 maintenance for advanced pancreatic adenocarcinoma: a single-arm phase II trial
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits