Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors
Abstract
:1. Introduction
2. Hydroxychloroquine Clinical Trials
3. New Potent Autophagy Inhibitors
4. Conclusions
Conflicts of Interest
References
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Treatment | Condition | Phase | Trial Reference # at ClinicalTrials.gov |
---|---|---|---|
HCQ + sunitinib malate | Adult solid neoplasm | I | NCT00813423 |
HCQ + vorinostat | Malignant solid tumor | I | NCT01023737 |
HCQ + sirolimus or vorinostat | Advanced cancers | I | NCT01266057 |
HCQ + Protein kinase B (Akt) inhibitor MK-2206 dihydrochloride (MK2206) | Advanced cancers | I | NCT01480154 |
HCQ as a single agent | Estrogen receptor positive breast cancer | I | NCT02414776 |
HCQ + gemcitabine | Advanced adenocarcinoma | I/II | NCT01506973 |
HCQ + Interleukin 2(IL-2) | Renal cell carcinoma | I/II | NCT01550367 |
HCQ + vorinostat | Colorectal cancer | I/II | NCT02316340 |
HCQ + gemcitabine/carboplatin | Small cell lung cancer | I/II | NCT02722369 |
HCQ + capecitabine | Pancreatic carcinoma | II | NCT01494155 |
HCQ as a single agent | Prostate cancer | II | NCT00726596 |
HCQ + Abraxane and gemcitabine | Pancreatic carcinoma | II | NCT01978184 |
Name | Mechanism | Target Point | References |
---|---|---|---|
3-Methyladenine | phosphoinositide3-kinase (PI3) inhibitor | Autophagosome formation | [18] |
Wortmannin | PI3-kinase inhibitor | Autophagosome formation | [19] |
LY294002 | PI3-kinase inhibitor | Autophagosome formation | [20] |
SBI-0206965 | Unc-51-like kinase 1 (ULK1) Inhibitor | Autophagosome formation | [51] |
Spautin-1 | ubiquitin-specific peptidases (USP10) and (USP13) inhibitor | Autophagosome formation | [15,52,53] |
SAR405 | Vacuolar Protein Sorting Protein 18 and 34 (Vps18 and Vps34) inhibitor | Autophagosome formation | [22,54] |
NSC185058 | autophagy-related gene 4 (ATG4) inhibitor | Autophagosome formation | [55] |
Verteporfin | Unknown | Autophagosome formation and accumulation | [39,56] |
ROC325 | Unknown | Lysosome | [58,59] |
Lys05 | Unknown | Lysosome | [8,36,47,48,49] |
Chloroquine | Unknown | Lysosome | [29,30,37] |
Hydroxychloroquine | Unknown | Lysosome | [30,31,35,37,60] |
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Chude, C.I.; Amaravadi, R.K. Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors. Int. J. Mol. Sci. 2017, 18, 1279. https://doi.org/10.3390/ijms18061279
Chude CI, Amaravadi RK. Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors. International Journal of Molecular Sciences. 2017; 18(6):1279. https://doi.org/10.3390/ijms18061279
Chicago/Turabian StyleChude, Cynthia I., and Ravi K. Amaravadi. 2017. "Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors" International Journal of Molecular Sciences 18, no. 6: 1279. https://doi.org/10.3390/ijms18061279