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Non-competitive overactivation of IGF-1R signaling (through mutations) support NSCLC resistance to xentuzumab (BI 836845), a monoclonal antibody targeting both IGF-1 and IGF-2 ( Similarly, other small molecule inhibitors and antibody-drug conjugates are being tested in other types of cancers where the IGF-1R/PI3K and AXL signaling pathways have also recently attracted attention, including in primary bone cancers where they play a major role in oncogenesis, cell differentiation and fate, metastasis, and drug resistance ( in vivo and in vitro and overcame resistance to cisplatin in ovarian cancer cell lines ( 6.4 IGF-1R tumorigenic interactions with other receptor tyrosine kinases 6.4.1 IGF-1R and FGFR1 axes Manipulating the IGF-1R signaling pathway has been viewed by many scholars as a potential breakthrough in anticancer therapies