SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer

Recurrent tumors that are resistant to conventional chemotherapy are a major challenge of ovarian cancer treatment. A better understanding of the underlying molecular mechanisms of chemoresistance is critical for developing more effective targeted therapies for ovarian cancer. In this study, we anal...

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Published in:Cancers 2025-01, Vol.17 (2), p.244
Main Authors: Jiang, Ziyan, Bi, Fangfang, Ge, Zhiping, Mansolf, Miranda, Hartwich, Tobias M P, Kolesnyk, Viktoriia, Yang, Kevin, Park, Wonmin, Kim, Dongin, Grechukhina, Olga, Hui, Pei, Kim, Sang Wun, Yang-Hartwich, Yang
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Language:English
Subjects:
Breast cancer
Cancer therapies
Cell proliferation
Cells
Chemokines
Chemoresistance
Drug resistance
Epidermal growth factor
Fibroblast growth factor receptor 4
Fibroblasts
Gene amplification
Growth factors
Kinases
Ligands
Medical prognosis
Molecular modelling
Ovarian cancer
Patients
Platinum
Proteins
Review boards
Tumors
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container_issue 2
container_start_page 244
container_title Cancers
container_volume 17
creator Jiang, Ziyan
Bi, Fangfang
Ge, Zhiping
Mansolf, Miranda
Hartwich, Tobias M P
Kolesnyk, Viktoriia
Yang, Kevin
Park, Wonmin
Kim, Dongin
Grechukhina, Olga
Hui, Pei
Kim, Sang Wun
Yang-Hartwich, Yang
description Recurrent tumors that are resistant to conventional chemotherapy are a major challenge of ovarian cancer treatment. A better understanding of the underlying molecular mechanisms of chemoresistance is critical for developing more effective targeted therapies for ovarian cancer. In this study, we analyzed the transcriptomic profiles of thirteen pairs of matching primary and recurrent ovarian cancers to identify genes that were upregulated in the recurrent tumors. Among these genes, we identified sortilin-related receptor 1 (SORL1) and its role in promoting carboplatin resistance through regulating the stability of epidermal growth factor receptor (EGFR) and fibroblast growth receptor 4 (FGFR4) using ovarian cancer models in vitro and in vivo. We further identified that an anti-SORL1 antibody inhibited the pro-tumor functions of SORL1. Our data showed that a selective inhibitor of FGFR4, FGF401, can improve the therapeutic efficacy of carboplatin in a xenograft mouse model of ovarian cancer. This study has demonstrated the therapeutic potential of targeting the SORL1/FGFR4 pathway to improve the chemoresponse of patients with recurrent and/or resistant ovarian cancer.
doi_str_mv 10.3390/cancers17020244
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subjects Breast cancer
Cancer therapies
Cell proliferation
Cells
Chemokines
Chemoresistance
Drug resistance
Epidermal growth factor
Fibroblast growth factor receptor 4
Fibroblasts
Gene amplification
Growth factors
Kinases
Ligands
Medical prognosis
Molecular modelling
Ovarian cancer
Patients
Platinum
Proteins
Review boards
Tumors
title SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer
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