Details

Autor(en) / Beteiligte

• Roche, Sandra
• Gaule, Patricia
• Winrow, Deirdre
• Mukherjee, Nupur
• O'Neill, Fiona
• Conlon, Neil T
• Meiller, Justine
• Collins, Denis M
• Canonici, Alexandra
• Fawsi, Mohammed Ibrahim
• Estepa-Fernández, Alejandra
• Madden, Stephen F
• Crown, John
• O'Donovan, Norma
• Eustace, Alex J
• Agoulnik, Irina U.

Titel

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

Ist Teil von

• PloS one, 2023-03, Vol.18 (3), p.e0282512-e0282512

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.