ArticleAutophagy2015
Targeting Hedgehog signaling pathway and autophagy overcomes drug resistance of BCR-ABL-positive chronic myeloid leukemia.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 90 citations in OpenAlex.
- Targeting autophagy and metabolism for ewing sarcoma.Molecular biology reports · 2025Review
- GANT61 Modulates Autophagy and Lipid Metabolism in Ovarian Cancer.Cell proliferation · 2025Article
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- Analyzing Hedgehog pathway-related genes: insights into breast cancer tumor microenvironment and prognostic implications.Frontiers in immunology · 2025Article
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- Mechanism of Drug Resistance to First-Line Chemotherapeutics Mediated by TXNDC17 in Neuroblastomas.Cancer reports (Hoboken, N.J.) · 2024Article
- A Multi-Omics Prognostic Model Capturing Tumor Stemness and the Immune Microenvironment in Clear Cell Renal Cell Carcinoma.Biomedicines · 2024Article
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Cancer Stem Cells from Definition to Detection and Targeted Drugs.International journal of molecular sciences · 2024Review
- HDAC inhibitor chidamide overcomes drug resistance in chronic myeloid leukemia with the T315i mutation through the Akt-autophagy pathway.Human cell · 2023Article
- Article
- MCancer science · 2022Article
- The crosstalk between sonodynamic therapy and autophagy in cancer.Frontiers in pharmacology · 2022Review
- The hedgehog pathway in hematopoiesis and hematological malignancy.Frontiers in oncology · 2022Review
- Hedgehog Signaling in Myeloid Malignancies.Cancers · 2021Review
- Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer.Cell death & disease · 2021Article
- Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment.Acta pharmaceutica Sinica. B · 2021Review
- Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents.Signal transduction and targeted therapy · 2021Review
- Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The frontline tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, drug resistance is the major clinical challenge in the treatment of CML. The Hedgehog (Hh) signaling pathway and autophagy are both related to tumorigenesis, cancer therapy, and drug resistance. This study was conducted to explore whether the Hh pathway could regulate autophagy in CML cells and whether simultaneously regulating the Hh pathway and autophagy could induce cell death of drug-sensitive or -resistant BCR-ABL(+) CML cells. Our results indicated that pharmacological or genetic inhibition of Hh pathway could markedly induce autophagy in BCR-ABL(+) CML cells. Autophagic inhibitors or ATG5 and ATG7 silencing could significantly enhance CML cell death induced by Hh pathway suppression. Based on the above findings, our study demonstrated that simultaneously inhibiting the Hh pathway and autophagy could markedly reduce cell viability and induce apoptosis of imatinib-sensitive or -resistant BCR-ABL(+) cells. Moreover, this combination had little cytotoxicity in human peripheral blood mononuclear cells (PBMCs). Furthermore, this combined strategy was related to PARP cleavage, CASP3 and CASP9 cleavage, and inhibition of the BCR-ABL oncoprotein. In conclusion, this study indicated that simultaneously inhibiting the Hh pathway and autophagy could potently kill imatinib-sensitive or -resistant BCR-ABL(+) cells, providing a novel concept that simultaneously inhibiting the Hh pathway and autophagy might be a potent new strategy to overcome CML drug resistance.
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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.