ArticleOncotarget2015
Mechanisms for autophagy modulation by isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.International journal of cancer · 2025Pooled it
- Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.International journal of molecular sciences · 2023Pooled it
- Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.Nature communications · 2026Article
- Impact of fixed phosphorus position on activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2025Article
- α-Amino bisphosphonate triazoles serve as GGDPS inhibitors.Bioorganic & medicinal chemistry letters · 2024Article
- Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy.Molecular cancer therapeutics · 2024Review
- Autophagy-related mechanisms for treatment of multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target.Clinical and translational medicine · 2023Review
- Geranylgeranyl diphosphate synthase inhibitor and proteasome inhibitor combination therapy in multiple myeloma.Experimental hematology & oncology · 2022Article
- Impact of α-modifications on the activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2021Article
- Bisphosphonates for delivering drugs to bone.British journal of pharmacology · 2021Review
- ω-Hydroxy isoprenoid bisphosphonates as linkable GGDPS inhibitors.Bioorganic & medicinal chemistry letters · 2019Article
- Inhibition of thioredoxin activates mitophagy and overcomes adaptive bortezomib resistance in multiple myeloma.Journal of hematology & oncology · 2018Article
- N6-isopentenyladenosine dual targeting of AMPK and Rab7 prenylation inhibits melanoma growth through the impairment of autophagic flux.Cell death and differentiation · 2018Article
- α-Methylation enhances the potency of isoprenoid triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2018Article
- Novel tropolones induce the unfolded protein response pathway and apoptosis in multiple myeloma cells.Oncotarget · 2017Article
- Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors.Molecules (Basel, Switzerland) · 2017Review
- Bishomoisoprenoid triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase.Bioorganic & medicinal chemistry · 2017Article
- Olefin Isomers of a Triazole Bisphosphonate Synergistically Inhibit Geranylgeranyl Diphosphate Synthase.Molecular pharmacology · 2017Article
- Multi-kinase inhibitors interact with sildenafil and ERBB1/2/4 inhibitors to kill tumor cells in vitro and in vivo.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Multiple myeloma (MM) is characterized by the production of monoclonal protein (MP). We have shown previously that disruption of the isoprenoid biosynthetic pathway (IBP) causes a block in MP secretion through a disruption of Rab GTPase activity, leading to an enhanced unfolded protein response and subsequent apoptosis in MM cells. Autophagy is induced by cellular stressors including nutrient deprivation and ER stress. IBP inhibitors have been shown to have disparate effects on autophagy. Here we define the mechanisms underlying the differential effects of IBP inhibitors on autophagic flux in MM cells utilizing specific pharmacological inhibitors. We demonstrate that IBP inhibition induces a net increase in autophagy as a consequence of disruption of isoprenoid biosynthesis which is not recapitulated by direct geranylgeranyl transferase inhibition. IBP inhibitor-induced autophagy is a cellular defense mechanism as treatment with the autophagy inhibitor bafilomycin A1 enhances the cytotoxic effects of GGPP depletion, but not geranylgeranyl transferase inhibition. Immunofluorescence microscopy studies revealed that IBP inhibitors disrupt ER to Golgi trafficking of monoclonal light chain protein and that this protein is not a substrate for alternative degradative pathways such as aggresomes and autophagosomes. These studies support further development of specific GGTase II inhibitors as anti-myeloma agents.
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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.