ArticleBlood2012
Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 172 citations in OpenAlex.
- Disrupting adaptive proteostasis to overcome proteasome inhibitor resistance.Haematologica · 2026Article
- Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.Haematologica · 2026Article
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Personalized neoantigen vaccines as early intervention in untreated patients with lymphoplasmacytic lymphoma: a non-randomized phase 1 trial.Nature communications · 2024Article
- Functional Investigation ofCancers · 2024Article
- Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs.Scientific reports · 2024Article
- Different evasion strategies in multiple myeloma.Frontiers in immunology · 2024Review
- Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors.JAMA network open · 2023Article
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Autophagy and Apoptosis: Current Challenges of Treatment and Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2022Review
- Metabolic cross-talk within the bone marrow milieu: focus on multiple myeloma.Experimental hematology & oncology · 2022Review
- Bone-Targeted Bortezomib Inhibits Bortezomib-Resistant Multiple Myeloma in Mice by Providing Higher Levels of Bortezomib in Bone.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.Molecules (Basel, Switzerland) · 2022Review
- Tetrahydrobiopterin induces proteasome inhibitor resistance and tumor progression in multiple myeloma.Medical oncology (Northwood, London, England) · 2022Article
- Advances in the molecular characterization of multiple myeloma and mechanism of therapeutic resistance.Frontiers in oncology · 2022Review
- Drug resistance and minimal residual disease in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Mucin 20 modulates proteasome capacity through c-Met signalling to increase carfilzomib sensitivity in mantle cell lymphoma.Journal of cellular and molecular medicine · 2021Article
- Bisphosphonates for delivering drugs to bone.British journal of pharmacology · 2021Review
- The fatty acid elongase ELOVL6 regulates bortezomib resistance in multiple myeloma.Blood advances · 2021Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Proteasome inhibition with bortezomib is a validated approach to the treatment of multiple myeloma, but drug resistance often emerges and limits its utility in the retreatment setting. To begin to identify some of the mechanisms involved, we developed bortezomib-resistant myeloma cell lines that, unlike previously reported models, showed no β5 subunit mutations. Instead, up-regulation of the insulin-like growth factor (IGF)-1 axis was identified, with increased autocrine and paracrine secretion of IGF-1, leading to increased activation of the IGF-1 receptor (IGF-1R). Exogenous IGF-1 reduced cellular sensitivity to bortezomib, whereas pharmacologic or small hairpin RNA-mediated IGF-1R suppression enhanced bortezomib sensitivity in cell lines and patient samples. In vitro studies with OSI-906, a clinically relevant dual IGF-1R and insulin receptor inhibitor, showed it acted synergistically with bortezomib, and potently resensitized bortezomib-resistant cell lines and patient samples to bortezomib. Importantly, OSI-906 in combination with bortezomib also overcame bortezomib resistance in an in vivo model of myeloma. Taken together, these data support the hypothesis that signaling through the IGF-1/IGF-1R axis contributes to acquired bortezomib resistance, and provide a rationale for combining bortezomib with IGF-1R inhibitors like OSI-906 to overcome or possibly prevent the emergence of bortezomib-refractory disease in the clinic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.