IGF-1R targeting in cancer - does sub-cellular localization matter?
IGF-1R targeting in cancer - does sub-cellular localization matter?
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DOI：
10.1186/s13046-023-02850-7
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发表时间：
2023-10-20
影响因子：
11.3
通讯作者：
Hegde, Rashmi S.
中科院分区：
文献类型：
--
作者：
Soni, Upendra K.;Jenny, Liam;Hegde, Rashmi S.
胰岛素样生长因子受体（IGF-1 R）是肿瘤学中最受关注的激酶靶点之一。然而，即使在一系列小分子和抗体疗法进入一系列实体瘤的临床试验之后，最初的承诺仍然没有实现。对IGF-1 R靶向药物的耐药性和毒性机制已被很好地分类，并且普遍认识到缺乏基于生物标志物的患者分层是以前临床试验的局限性。但是，还没有下一代治疗策略在临床上成功地利用了这种理解。目前，人们对在具有预测性生物标志物驱动的患者分层的组合治疗方案中重新访问IGF-1 R靶向治疗剂产生了兴趣。从早期临床试验中出现的一种这样的生物标志物是IGF-1 R的亚细胞定位。在提供了IGF-1 R的一些背景，其用药历史以及导致该靶点药物开发终止的试验之后，我们更深入地研究了IGF-1 R的亚细胞定位与对各类IGF-1 R靶向药物的易感性之间的相关性。在线版本包含补充材料，可通过10.1186/s13046-023-02850-7获得。
The insulin-like growth factor receptor (IGF-1R) was among the most intensively pursued kinase targets in oncology. However, even after a slew of small-molecule and antibody therapeutics reached clinical trials for a range of solid tumors, the initial promise remains unfulfilled. Mechanisms of resistance to, and toxicities resulting from, IGF-1R-targeted drugs are well-catalogued, and there is general appreciation of the fact that a lack of biomarker-based patient stratification was a limitation of previous clinical trials. But no next-generation therapeutic strategies have yet successfully exploited this understanding in the clinic. Currently there is emerging interest in re-visiting IGF-1R targeted therapeutics in combination-treatment protocols with predictive biomarker-driven patient-stratification. One such biomarker that emerged from early clinical trials is the sub-cellular localization of IGF-1R. After providing some background on IGF-1R, its drugging history, and the trials that led to the termination of drug development for this target, we look more deeply into the correlation between sub-cellular localization of IGF-1R and susceptibility to various classes of IGF-1R - targeted agents. The online version contains supplementary material available at 10.1186/s13046-023-02850-7.
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