IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer

Connie Bitelman; Rive Sarfstein; Menahem Sarig; Zohar Attias-Geva; Ami Fishman; Haim Werner; Ilan Bruchim

doi:10.1016/j.canlet.2013.02.009

IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer

Connie Bitelman
, Rive Sarfstein
, Menahem Sarig
, Zohar Attias-Geva
, Ami Fishman
, Haim Werner
, Ilan Bruchim^*

^*Corresponding author for this work

Human Molecular Genetics Biochemistry

Tel Aviv University
Meir Hospital Sapir Medical Center

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2 endometrial cancer. We found that MK-0646 treatment significantly decreased IGF1R expression. In addition, pretreatment with MK-0646 decreased the IGF1-induced phosphorylation of IGF1R, AKT and ERK. Apoptosis analyses showed that MK-0646 abolished the anti-apoptotic effect of IGF1. Furthermore, MK-0646 treatment abolished the IGF1-stimulatory effect on proliferation and enhanced the cytotoxic effect of cisplatin. These findings indicate that specific inhibition of IGF1R could be a useful therapeutic approach for Type 1 and Type 2 endometrial cancer.

Original language	English
Pages (from-to)	153-159
Number of pages	7
Journal	Cancer Letters
Volume	335
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2013.02.009
State	Published - 10 Jul 2013

Funding

Funders
Israel Cancer Research Fund
Meso Scale Diagnostics
Merck Sharp and Dohme

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Endometrial cancer
IGF1
IGF1 receptor
MK-0646
Uterine serous carcinoma

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10.1016/j.canlet.2013.02.009

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title = "IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer",

abstract = "This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2 endometrial cancer. We found that MK-0646 treatment significantly decreased IGF1R expression. In addition, pretreatment with MK-0646 decreased the IGF1-induced phosphorylation of IGF1R, AKT and ERK. Apoptosis analyses showed that MK-0646 abolished the anti-apoptotic effect of IGF1. Furthermore, MK-0646 treatment abolished the IGF1-stimulatory effect on proliferation and enhanced the cytotoxic effect of cisplatin. These findings indicate that specific inhibition of IGF1R could be a useful therapeutic approach for Type 1 and Type 2 endometrial cancer.",

keywords = "Endometrial cancer, IGF1, IGF1 receptor, MK-0646, Uterine serous carcinoma",

author = "Connie Bitelman and Rive Sarfstein and Menahem Sarig and Zohar Attias-Geva and Ami Fishman and Haim Werner and Ilan Bruchim",

note = "Funding Information: The authors wish to thank Merck, Sharp and Dohme (MSD, Israel) and the Israel Cancer Research Fund (ICRF, Montreal, Canada) for their generous support. Funding Information: This study was supported by a grant from Merck, Sharp and Dohme (MSD, Israel) to H.W., A.F., and I.B. None of the authors has received any payment or royalty from MSD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. I.B. and H.W. wish to thank the generous support of the Israel Cancer Research Fund (ICRF), Montreal, Canada. ",

year = "2013",

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doi = "10.1016/j.canlet.2013.02.009",

language = "אנגלית",

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T1 - IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer

AU - Bitelman, Connie

AU - Sarfstein, Rive

AU - Sarig, Menahem

AU - Attias-Geva, Zohar

AU - Fishman, Ami

AU - Werner, Haim

AU - Bruchim, Ilan

N1 - Funding Information: The authors wish to thank Merck, Sharp and Dohme (MSD, Israel) and the Israel Cancer Research Fund (ICRF, Montreal, Canada) for their generous support. Funding Information: This study was supported by a grant from Merck, Sharp and Dohme (MSD, Israel) to H.W., A.F., and I.B. None of the authors has received any payment or royalty from MSD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. I.B. and H.W. wish to thank the generous support of the Israel Cancer Research Fund (ICRF), Montreal, Canada.

PY - 2013/7/10

Y1 - 2013/7/10

N2 - This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2 endometrial cancer. We found that MK-0646 treatment significantly decreased IGF1R expression. In addition, pretreatment with MK-0646 decreased the IGF1-induced phosphorylation of IGF1R, AKT and ERK. Apoptosis analyses showed that MK-0646 abolished the anti-apoptotic effect of IGF1. Furthermore, MK-0646 treatment abolished the IGF1-stimulatory effect on proliferation and enhanced the cytotoxic effect of cisplatin. These findings indicate that specific inhibition of IGF1R could be a useful therapeutic approach for Type 1 and Type 2 endometrial cancer.

AB - This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2 endometrial cancer. We found that MK-0646 treatment significantly decreased IGF1R expression. In addition, pretreatment with MK-0646 decreased the IGF1-induced phosphorylation of IGF1R, AKT and ERK. Apoptosis analyses showed that MK-0646 abolished the anti-apoptotic effect of IGF1. Furthermore, MK-0646 treatment abolished the IGF1-stimulatory effect on proliferation and enhanced the cytotoxic effect of cisplatin. These findings indicate that specific inhibition of IGF1R could be a useful therapeutic approach for Type 1 and Type 2 endometrial cancer.

KW - Endometrial cancer

KW - IGF1

KW - IGF1 receptor

KW - MK-0646

KW - Uterine serous carcinoma

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AN - SCOPUS:84878447701

SN - 0304-3835

VL - 335

SP - 153

EP - 159

JO - Cancer Letters

JF - Cancer Letters

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ER -

IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer

Abstract

Funding

UN SDGs

Keywords

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