National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland.
Data Science Centre, Royal College of Surgeons in Ireland, Dublin, Ireland.
PLoS One. 2023 Mar 15;18(3):e0282512. doi: 10.1371/journal.pone.0282512. eCollection 2023.
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.
三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，比其他类型的乳腺癌有更少的成功治疗方法。胰岛素样生长因子受体 1（IGF1R）和胰岛素受体（IR）与 TNBC 的不良预后相关。针对 IGF1R 的治疗在临床上已经失败。我们旨在测试抑制 IR/IGF1R 是否是治疗 TNBC 的合理治疗方法。我们表明，尽管 TNBC 中表达 IGF1R 和 IR，但它们的表达与生存不良结局无关。此外，用抑制剂在多种 TNBC 细胞系中同时靶向 IR/IGF1R 并不能抑制细胞生长。Linsitinib 是 IGF1R 和 IR 的小分子抑制剂，它不能阻止肿瘤形成，也不能抑制体内肿瘤生长。综上所述，这些数据表明，尽管 IGF1R 和 IR 在 TNBC 中表达，但它们不是很好的治疗靶点。当靶向 IR/IGF1R 时，抗癌作用有限的一个潜在原因可能是因为 TNBC 中改变了多种信号通路。因此，靶向单个信号通路可能不足以抑制癌症生长。
