Open AccessPharmacological Inhibition of Insulin Growth Factor‐1 Receptor (IGF‐1R) Alone or in Combination With Ruxolitinib Shows Therapeutic Efficacy in Preclinical Myeloproliferative Neoplasm Models
Author(s) -
Basu Titiksha,
Bertrand Hannah,
Karantzelis Nikolaos,
Gründer Albert,
Pahl Heike L.
Publication year - 2021
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/hs9.0000000000000565
Subject(s) - ruxolitinib , myeloproliferative neoplasm , insulin like growth factor , medicine , pharmacology , growth factor , in vivo , cancer research , cytokine , receptor , biology , myelofibrosis , bone marrow , microbiology and biotechnology
Even after development of the JAK1/JAK2 inhibitor ruxolitinib, myeloproliferative neoplasm (MPN) patients require novel therapeutic options. While ruxolitinib can considerably improve quality of life and prolong survival, it does not modify the natural disease course in most patients. Moreover, resistance develops with prolonged use. Therefore, various combination treatments are currently being investigated. Published data provide a compelling rationale for the inhibition of insulin growth factor‐1 receptor (IGF‐1R) signaling in MPN. Here we report that genetic and pharmacological inhibition of IGF‐1R selectively reduced Jak2 V617F ‐driven cytokine‐independent proliferation ex vivo. Two different structurally unrelated IGF‐1R inhibitors ameliorated disease phenotype in a murine MPN model and significantly prolonged survival. Moreover, in mice, low‐dose ruxolitinib synergized with IGF‐1R inhibition to increase survival. Our data demonstrate preclinical efficacy of IGF‐1R inhibition in a murine MPN model.