Insulin-like growth factor 1 receptor (IGF-1R) (IGF-1R)

The Insulin-like growth factor 1 receptor (IGF-1R) is a transmembrane receptor tyrosine kinase essential for mediating the effects of insulin-like growth factors on cell growth and survival (UniProt: P08069). Upon ligand binding, IGF-1R undergoes autophosphorylation and activates intracellular signaling cascades, primarily the PI3K/Akt and Ras/MAPK pathways, which are pivotal for oncogenic transformation and resistance to apoptosis (PubMed: 19433553). In many cancers, IGF-1R is overexpressed, making it a significant therapeutic target for monoclonal antibodies like figitumumab. Clinical investigations into the combination of figitumumab and docetaxel were conducted to exploit potential synergistic effects in treating solid tumors, such as non-small cell lung cancer (PubMed: 21422404). These studies specifically monitored docetaxel exposure to ensure that IGF-1R inhibition did not adversely alter the metabolism or clearance of the chemotherapy agent, which is primarily processed by the CYP3A4 enzyme (ClinicalTrials.gov: NCT00596830). Although figitumumab showed promise in early trials, its development was halted after Phase III trials failed to demonstrate a survival benefit and revealed increased toxicity. The pharmacokinetic interaction studies confirmed that figitumumab does not significantly impact the systemic exposure of docetaxel, allowing for safe co-administration from a metabolic standpoint.

Other names

IGF1RCD221Insulin-like growth factor I receptorIGF-I receptorJTK13

Figitumumab is a fully human IgG2 monoclonal antibody that binds with high affinity to the extracellular domain of the Insulin-like growth factor 1 receptor (IGF-1R). This binding prevents the interaction of IGF-1R with its ligands, IGF-1 and IGF-2, and triggers the internalization and degradation of the receptor. Consequently, downstream signaling through the PI3K/Akt and MAPK pathways is inhibited, leading to reduced cell proliferation and increased apoptosis in tumor cells.