ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Dual Targeting of Protein Degradation Pathways with the Selective HDAC6 Inhibitor ACY-1215 and Bortezomib Is Synergistic in Lymphoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 90 citations in OpenAlex.
- Preclinical and clinical efficacy of the HDAC6 inhibitor ricolinostat in combination with BCR pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia.Blood cancer journal · 2026Article
- Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma.Scientific reports · 2025Article
- [HDAC6 inhibitor ACY-738 induces apoptosis and autophagy in diffuse large B-cell lymphoma cells through P53 acetylation].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-Translational Modifications and Protein-Protein Interactions.International journal of molecular sciences · 2025Review
- Microtubule acetylation and PERK activation facilitate eribulin-induced mitochondrial calcium accumulation and cell death.Cellular and molecular life sciences : CMLS · 2024Article
- The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?Biomedicines · 2024Review
- Review
- Update on histone deacetylase inhibitors in peripheral T-cell lymphoma (PTCL).Clinical epigenetics · 2023Review
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- Impact of Histone Modifications and Their Therapeutic Targeting in Hematological Malignancies.International journal of molecular sciences · 2022Review
- HDAC6: A unique HDAC family member as a cancer target.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition.Oncogene · 2022Article
- Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer.Frontiers in chemistry · 2022Review
- Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases.Frontiers in pharmacology · 2022Review
- Histone Modifications and Their Targeting in Lymphoid Malignancies.International journal of molecular sciences · 2021Review
- Romidepsin and lenalidomide-based regimens have efficacy in relapsed/refractory lymphoma: Combined analysis of two phase I studies with expansion cohorts.American journal of hematology · 2021Article
- Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.Oncogene · 2021Article
- Induction of synergistic non-apoptotic cell death by simultaneously targeting proteasomes with bortezomib and histone deacetylase 6 with ricolinostat in head and neck tumor cells.Oncology letters · 2021Article
- Review
- The regulation of miR-320a/XBP1 axis through LINC00963 for endoplasmic reticulum stress and autophagy in diffuse large B-cell lymphoma.Cancer cell international · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
purposePan-class histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform-selective HDAC inhibitors are emerging as potentially more targeted agents. HDAC6 is a class IIb deacetylase that facilitates misfolded protein transport to the aggresome for degradation. We investigated the mechanism and therapeutic impact of the selective HDAC6 inhibitor ACY-1215 alone and in combination with bortezomib in preclinical models of lymphoma. EXPERIMENTAL
designConcentration-effect relationships were defined for ACY-1215 across 16 lymphoma cell lines and for synergy with bortezomib. Mechanism was interrogated by immunoblot and flow cytometry. An in vivo xenograft model of DLBCL was used to confirm in vitro findings. A collection of primary lymphoma samples were surveyed for markers of the unfolded protein response (UPR).
resultsConcentration-effect relationships defined maximal cytotoxicity at 48 hours with IC50 values ranging from 0.9 to 4.7 μmol/L. Strong synergy was observed in combination with bortezomib. Treatment with ACY-1215 led to inhibition of the aggresome evidenced by acetylated α-tubulin and accumulated polyubiquitinated proteins and upregulation of the UPR. All pharmacodynamic effects were enhanced with the addition of bortezomib. Findings were validated in vivo where mice treated with the combination demonstrated significant tumor growth delay and prolonged overall survival. Evaluation of a collection of primary lymphoma samples for markers of the UPR revealed increased HDAC6, GRP78, and XBP-1 expression as compared with reactive lymphoid tissue.
conclusionsThese data are the first results to demonstrate that dual targeting of protein degradation pathways represents an innovative and rational approach for the treatment of lymphoma.
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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.