Abstract
The insulin-like growth factor-1 receptor (IGF-1R) has emerged as a critical target in oncology due to its pivotal role in tumor growth, progression, and therapeutic resistance. Despite encouraging preclinical findings, clinical trials utilizing IGF-1R inhibitors as monotherapies have largely been unsuccessful. Herein, we reviewed the available data with IGF-1R inhibitors and the potential of IGF-1R inhibitors when used in combination therapies, an approach supported by advances in precision medicine and immuno-oncology. We aimed to provide comprehensive analysis of the preclinical rationale underpinning the combination of IGF-1R inhibitors with immune checkpoint inhibitors, mTOR/AKT, CDK 4/6, BRAF/MEK, and DNA-damage repair pathway inhibitors. Furthermore, we discussed the development of biomarkers, such as IGF-1R expression levels and hyperglycemia, to predict therapeutic response. Despite initial challenges, the strategic integration of IGF-1R inhibitors within combination therapies holds promise for significantly improving patient outcomes by overcoming resistance. This review highlights the need for ongoing research to optimize these combination strategies and fully harness the therapeutic potential of IGF-1R inhibitors in cancer treatment.