title: Combination therapy approaches to target insulin-like growth factor receptor signaling in breast cancer.
abstract: Insulin-like growth factor receptor (IGF1R) signaling as a therapeutic target has been widely studied and clinically tested. Despite the vast amount of literature supporting the biological role of IGF1R in breast cancer, effective clinical translation in targeting its activity as a cancer therapy has not been successful. The intrinsic complexity of cancer cell signaling mediated by many tyrosine kinase growth factor receptors that work together to modulate each other and intracellular downstream mediators in the cell highlights that studying IGF1R expression and activity as a prognostic factor and therapeutic target in isolation is certainly associated with problems. This review discusses the current literature and clinical trials associated with IGF-1 signaling and attempts to look at new ways of designing novel IGF1R-directed breast cancer therapy approaches to target its activity  and/or intracellular downstream signaling pathways in IGF1R-expressing breast cancers.
authors.affiliation: Kolling Institute of Medical ResearchUniversity of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia aleksandra.ochnik@sydney.edu.au.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Ochnik
authors.affiliation: Kolling Institute of Medical ResearchUniversity of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baxter
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D057285:Precision Medicine / Q000379:methods; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1
keywords: breast cancer; insulin-like growth factor receptor; targeted therapies and sphingosine kinase