This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Carew JS, Nawrocki ST. Drain the lysosome: development of the novel orally available autophagy inhibitor ROC-325. Autophagy. 2017;13:765–6.
Mahalingam D, Mita M, Sarantopoulos J, Wood L, Amaravadi RK, Davis LE, et al. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy. 2014;10:1403–14.
Chude CI, Amaravadi RK. Targeting autophagy in cancer: update on clinical trials and novel inhibitors. Int J Mol Sci. 2017;18. pii: E1279.
Carew JS, Espitia CM, Esquivel JA 2nd, Mahalingam D, Kelly KR, Reddy G, et al. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011;286:6602–13.
Carew JS, Espitia CM, Zhao W, Han Y, Visconte V, Phillips J, et al. Disruption of autophagic degradation with ROC-325 antagonizes renal cell carcinoma pathogenesis. Clin Cancer Res. 2017;23:2869–79.
Visconte V, Przychodzen B, Han Y, Nawrocki ST, Thota S, Kelly KR, et al. Complete mutational spectrum of the autophagy interactome: a novel class of tumor suppressor genes in myeloid neoplasms. Leukemia. 2017;31:505–10.
Ornstein MC, Mukherjee S, Sekeres MA. More is better: combination therapies for myelodysplastic syndromes. Best Pr Res Clin Haematol. 2015;28:22–31.
Madanat Y, Sekeres MA. Optimizing the use of hypomethylating agents in myelodysplastic syndromes: Selecting the candidate, predicting the response, and enhancing the activity. Semin Hematol. 2017;54:147–53.
Romano A, Giallongo C, La Cava P, Parrinello NL, Chiechi A, Vetro C, et al. Proteomic analysis reveals autophagy as pro-survival pathway elicited by long-term exposure with 5-azacitidine in high-risk myelodysplasia. Front Pharm. 2017;8:204.
Robert G, Auberger P. Azacitidine resistance caused by LAMP2 deficiency: a therapeutic window for the use of autophagy inhibitors in MDS/AML patients? Autophagy. 2019;15:927–9.
Acknowledgements
This project was supported by grants from the National Cancer Institute (R01CA172443 to JSC and R01CA190789 to STN) and the University of Arizona Cancer Center Support Grant P30CA023074.
Author information
Authors and Affiliations
Contributions
STN contributed to the study design, performed experiments, analyzed and interpreted data, and wrote the paper. YH, VV, BP, and CME performed the experiments, analyzed and interpreted the data, and contributed to the paper preparation; analyzed and interpreted data and participated in the paper preparation. JP contributed to ROC-325 design and synthesis. FA, AA, HEC, KRK, MAS, and JPM consented patients to provide primary specimens in support of the study and participated in the data analysis and the paper preparation. JSC directed the study, performed the experiments, contributed to the data analysis and paper preparation. All authors approved the paper before submission.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Nawrocki, S.T., Han, Y., Visconte, V. et al. The novel autophagy inhibitor ROC-325 augments the antileukemic activity of azacitidine. Leukemia 33, 2971–2974 (2019). https://doi.org/10.1038/s41375-019-0529-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41375-019-0529-2
This article is cited by
-
Translatome proteomics identifies autophagy as a resistance mechanism to on-target FLT3 inhibitors in acute myeloid leukemia
Leukemia (2022)
-
Mitochondrial metabolism as a target for acute myeloid leukemia treatment
Cancer & Metabolism (2021)
-
Moving beyond hydroxychloroquine: the novel lysosomal autophagy inhibitor ROC-325 shows significant potential in preclinical studies
Cancer Communications (2019)