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Critical Reviews™ in Eukaryotic Gene Expression
Factor de Impacto: 2.156 Factor de Impacto de 5 años: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Imprimir: 1045-4403
ISSN En Línea: 2162-6502

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Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.2020032762
pages 121-123

Lysosome AKT Targeting in Metastatic Cancer

Ziv Radisavljevic
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115


Metastatic cancer is caused by hyperactivated lysosomes. Such activation causes a fungus, Aspergillus fumigatus, to permanently activate the AKT gene network that controls the lysosome through positive feedback loops. Targeting such a network by the redox balance change, and with an antifungal medication eliminates the metastatic phenotype, the complexity and robustness of the cancer. This principal mechanism of gene targeting, which suppressed metastasis of unknown origin, was observed clinically.


  1. Radisavljevic Z. AKT as locus of cancer unknown primary site. J Cell Biochem. 2016;117:1066-8.

  2. Radisavljevic Z. Lysosome activates AKT inducing cancer and metastasis. J Cell Biochem. 2019;120:12123-7. 13. doi: 10.1002/jcb.2875242.

  3. Radisavljevic Z. Nitric oxide suppression triggers apoptosis through the FKHRL1 (FOXO3a)/ROCK kinase pathway in human breast carcinoma cells. Cancer. 2003;97:1358-63.

  4. Radisavljevic Z. Locus of fragility in robust breast cancer system. J Cell Biochem. 2004;92:1020-4.

  5. Radisavljevic Z. Inactivated tumor suppressor Rb by nitric oxide promotes mitosis in human breast cancer cells. J Cell Biochem. 2004;92:1-5.

  6. Radisavljevic Z. AKT as locus of fragility in robust cancer system. J Cell Biochem. 2008;104:2071-7.

  7. Radisavljevic Z. AKT as locus of cancer angiogenic robustness and fragility. J Cell Physiol. 2013;228:21-4.

  8. Radisavljevic Z. AKT as locus of cancer positive feedback loops and extreme robustness. J Cell Physiol. 2013;228:522-4.

  9. Radisavljevic Z. AKT as locus of cancer multidrug resistance and fragility. J Cell Physiol. 2013;228:671-4.

  10. Radisavljevic Z. AKT as locus of cancer phenotype. J Cell Biochem. 2015;116:1-5.

  11. Radisavljevic Z. AKT as locus of cancer positive loops conversion and chemotherapy. Crit Rev Eukaryot Gene Expr. 2015;25:199-202.

  12. Radisavljevic Z. AKT as locus of hydrogen bond network in cancer. J Cell Biochem. 2018;119:130-3.

  13. Radisavljevic Z. Muon disrupts AKT hydrogen bond network in cancer. J Cell Physiol. 2019;234:7994-8. doi: 10.1002/jcp.27554.

  14. Radisavljevic Z, Avraham H, Avraham S. Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase/AKT/nitric oxide pathway and modulates migration of brain microvascular endothelial cells. J Biol Chem. 2000;275:20770-4.

  15. Hirata N, Suizu F, Matsuda-Lennikov M, Tanaka T, Edamura T, Ishigaki S, Donia T, Lithanatudom P, Obuse C, Iwanaga T, Noguchi M. Functional characterization of lysosomal interaction of Akt with VRK2. Oncogene. 2018;37:5367-86.

  16. Varadhachary GR, Raber MN. Cancer of unknown primary site. N Engl J Med. 2014;371:757-65. doi: 10.1056/ NEJMra1303917.

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