Preclinical evaluation of Insulin-like growth factor receptor 1 (IGF1R) and Insulin Receptor (IR) as a therapeutic targets in triple negative breast cancer

被引：7

作者：

Roche, Sandra ^{[1
]}

Gaule, Patricia ^{[1
]}

Winrow, Deirdre ^{[1
]}

Mukherjee, Nupur ^{[1
]}

O'Neill, Fiona ^{[1
]}

Conlon, Neil T. T. ^{[1
]}

Meiller, Justine ^{[1
]}

Collins, Denis M. M. ^{[1
]}

Canonici, Alexandra ^{[1
]}

Fawsi, Mohammed Ibrahim ^{[1
]}

Estepa-Fernandez, Alejandra ^{[1
]}

Madden, Stephen F. F. ^{[2
]}

Crown, John ^{[1
,3
]}

O'Donovan, Norma ^{[1
]}

Eustace, Alex J. J. ^{[1
]}

机构：

[1] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin, Ireland

[2] Royal Coll Surgeons Ireland, Data Sci Ctr, Dublin, Ireland

[3] St Vincents Univ Hosp, Dept Med Oncol, Dublin, Ireland

来源：

PLOS ONE | 2023年 / 18卷 / 03期

基金：

爱尔兰科学基金会;

关键词：

DUAL INHIBITOR; PHASE-I; IGF-1; RECEPTOR; OSI-906; LINSITINIB; INTERMITTENT; PACLITAXEL; PI3K;

D O I：

10.1371/journal.pone.0282512

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Triple Negative Breast Cancer (TNBC), a subtype of breast cancer, has fewer successful therapeutic therapies than other types of breast cancer. Insulin-like growth factor receptor 1 (IGF1R) and the Insulin receptor (IR) are associated with poor outcomes in TNBC. Targeting IGF1R has failed clinically. We aimed to test if inhibiting both IR/IGF1R was a rationale therapeutic approach to treat TNBC. We showed that despite IGF1R and IR being expressed in TNBC, their expression is not associated with a negative survival outcome. Furthermore, targeting both IR/IGF1R with inhibitors in multiple TNBC cell lines did not inhibit cell growth. Linsitinib, a small molecule inhibitor of both IGF1R and IR, did not block tumour formation and had no effect on tumour growth in vivo. Cumulatively these data suggest that while IGF1R and IR are expressed in TNBC, they are not good therapeutic targets. A potential reason for the limited anti-cancer impact when IR/IGF1R was targeted may be because multiple signalling pathways are altered in TNBC. Therefore, targeting individual signalling pathways may not be sufficient to inhibit cancer growth.

引用

页数：17

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