The effects of co-administration of Erlotinib and Apatinib in the treatment oesophageal Squamous Cell Carcinoma

Lin, Y; Zou, Q; Chen, H; Cui, Y; Chen, S

The effects of co-administration of Erlotinib and Apatinib in the treatment oesophageal Squamous Cell Carcinoma

Lin, Y

Zou, Q Chen, H Cui, Y Chen, S

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Publisher:: Elsevier
Publication Type:: Conference Proceeding
Citation:: Annals of Oncology, 2021, 32, pp. S187-S187
Issue Date:: 2021-06-30

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Field	Value	Language
dc.contributor.author	Lin, Y https://orcid.org/0000-0002-4637-9701
dc.contributor.author	Zou, Q
dc.contributor.author	Chen, H
dc.contributor.author	Cui, Y
dc.contributor.author	Chen, S
dc.date	2021-06-30
dc.date.accessioned	2021-07-06T13:18:57Z
dc.date.available	2021-04-16
dc.date.available	2021-07-06T13:18:57Z
dc.date.issued	2021-06-30
dc.identifier.citation	Annals of Oncology, 2021, 32, pp. S187-S187
dc.identifier.issn	0923-7534
dc.identifier.uri	http://hdl.handle.net/10453/149837
dc.description.abstract	Background: Epidermal growth factor receptor (EGFR) and vascular EGFR (VEGFR) molecular characteristics have significant relevance to patient prognosis. The extensive crosstalk between EGFR and VEGFR signaling in oesophageal cancer provides a rationale for joint targeting of the two pathways using Erlotinib plus Apatinib. The aim of the current study was to investigate the clinical potentials and the underlying mechanism for the combinational use of Erlotinib and Apatinib in the treatment of oesophageal squamous cell carcinoma (ESCC) using our established ESCC patient-derived tumour xenograft models. Methods: According to the EGFR copy number gain (CNG) and EGFR mutation status, we established preclinical models which became refractory to Erlotinib. We then evaluated the effects of Apatinib, Erlotinib, and Erlotinib plus Apatinib on EGFR (mut+) xenograft model and EGFR (mut-) xenograft models. Results: The combined administration of Erlotinib and Apatinib showed strong tumour inhibiting effects on EGFR (mut+) ESCC xenografts. When Erlotinib or Apatinib was used alone, the ESCC tumour inhibitory effects were significantly weaker. In comparison, Erlotinib and Apatinib together were exclusively cytostatic with no more activity than either drug alone in the EGFR (mut-) xenografts. Conclusions: Our data demonstrates that combined therapy with Erlotinib and Apatinib shows promising efficacy in the treatment of ESCC in a xenograft model of EGFR (Mut+). Furthermore, reinduction of VEGF and subsequent VEGF-dependent tumour growth has been suggested as one of the major mechanisms of acquired resistance to Erlotinib. These findings provide a rationale for further clinical trials of the oesophageal cancer patients with mutant EGFR.
dc.language	en
dc.publisher	Elsevier
dc.relation.ispartof	Annals of Oncology
dc.relation.isbasedon	10.1016/j.annonc.2021.05.317
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.title	The effects of co-administration of Erlotinib and Apatinib in the treatment oesophageal Squamous Cell Carcinoma
dc.type	Conference Proceeding
utslib.citation.volume	32
utslib.location.activity	Virtual
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	true
dc.date.updated	2021-07-06T13:18:56Z
pubs.finish-date	2021-07-03
pubs.publication-status	Published
pubs.start-date	2021-06-30
pubs.volume	32

Abstract:

Background: Epidermal growth factor receptor (EGFR) and vascular EGFR (VEGFR) molecular characteristics have significant relevance to patient prognosis. The extensive crosstalk between EGFR and VEGFR signaling in oesophageal cancer provides a rationale for joint targeting of the two pathways using Erlotinib plus Apatinib. The aim of the current study was to investigate the clinical potentials and the underlying mechanism for the combinational use of Erlotinib and Apatinib in the treatment of oesophageal squamous cell carcinoma (ESCC) using our established ESCC patient-derived tumour xenograft models. Methods: According to the EGFR copy number gain (CNG) and EGFR mutation status, we established preclinical models which became refractory to Erlotinib. We then evaluated the effects of Apatinib, Erlotinib, and Erlotinib plus Apatinib on EGFR (mut+) xenograft model and EGFR (mut-) xenograft models. Results: The combined administration of Erlotinib and Apatinib showed strong tumour inhibiting effects on EGFR (mut+) ESCC xenografts. When Erlotinib or Apatinib was used alone, the ESCC tumour inhibitory effects were significantly weaker. In comparison, Erlotinib and Apatinib together were exclusively cytostatic with no more activity than either drug alone in the EGFR (mut-) xenografts. Conclusions: Our data demonstrates that combined therapy with Erlotinib and Apatinib shows promising efficacy in the treatment of ESCC in a xenograft model of EGFR (Mut+). Furthermore, reinduction of VEGF and subsequent VEGF-dependent tumour growth has been suggested as one of the major mechanisms of acquired resistance to Erlotinib. These findings provide a rationale for further clinical trials of the oesophageal cancer patients with mutant EGFR.

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