ArticleJournal for immunotherapy of cancer2021
IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- The advent of precision nutrigeroscience in cancer: from clinic towards molecular biology.Journal of advanced research · 2026Review
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- Insulin and Insulin-like Growth Factor 1 Signaling as a Modulator of MYC Expression in the Meibomian Gland.Biomedicines · 2026Article
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- Article
- IGF1/IGF1R signaling promotes the expansion of liver CSCs and serves as a potential therapeutic target in HCC.Discover oncology · 2025Article
- Fasting and fasting-mimicking conditions in the cancer immunotherapy era.Journal of physiology and biochemistry · 2025Review
- The inducible role of autophagy in cell death: emerging evidence and future perspectives.Cell communication and signaling : CCS · 2025Review
- Oleanolic Acid Slows Down Aging Through IGF-1 Affecting the PI3K/AKT/mTOR Signaling Pathway.Molecules (Basel, Switzerland) · 2025Article
- Inhibition of programmed cell death by melanoma cell subpopulations reveals mechanisms of melanoma metastasis and potential therapeutic targets.Discover oncology · 2025Article
- The Common Hallmarks and Interconnected Pathways of Aging, Circadian Rhythms, and Cancer: Implications for Therapeutic Strategies.Research (Washington, D.C.) · 2025Review
- The Ambiguous Role of HMGB1 Across the Hallmarks of Aging: A Narrative Review.Clinical interventions in aging · 2025Review
- Hypoxia signature derived from tumor-associated endothelial cells predict prognosis in gastric cancer.Frontiers in cell and developmental biology · 2025Article
- Advances in the role of the IGF signaling system in myelodysplastic syndromes and acute myeloid leukemia.Frontiers in oncology · 2025Review
- Targeting immunogenic cell stress and death for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma.Signal transduction and targeted therapy · 2024Article
- Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes.Molecular cancer · 2024Review
- Prognosis and therapeutic significance of IGF-1R-related signaling pathway gene signature in glioma.Frontiers in cell and developmental biology · 2024Article
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Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundPharmacological autophagy enhancement constitutes a preclinically validated strategy for preventing or treating most major age-associated diseases. Driven by this consideration, we performed a high-content/high-throughput screen on 65 000 distinct compounds on a robotized fluorescence microscopy platform to identify novel autophagy inducers.
resultsHere, we report the discovery of picropodophyllin (PPP) as a potent inducer of autophagic flux that acts on-target, as an inhibitor of the tyrosine kinase activity of the insulin-like growth factor-1 receptor (IGF1R). Thus, PPP lost its autophagy-stimulatory activity in cells engineered to lack IGF1R or to express a constitutively active AKT serine/threonine kinase 1 (AKT1) mutant. When administered to cancer-bearing mice, PPP improved the therapeutic efficacy of chemoimmunotherapy with a combination of immunogenic cytotoxicants and programmed cell death 1 (PDCD1, better known as PD-1) blockade. These PPP effects were lost when tumors were rendered PPP-insensitive or autophagy-incompetent. In combination with chemotherapy, PPP enhanced the infiltration of tumors by cytotoxic T lymphocytes, while reducing regulatory T cells. In human triple-negative breast cancer patients, the activating phosphorylation of IGF1R correlated with inhibited autophagy, an unfavorable local immune profile, and poor prognosis.
conclusionAltogether, these results suggest that IGF1R may constitute a novel and druggable therapeutic target for the treatment of cancer in conjunction with chemoimmunotherapies.
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