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PMID: 21440002 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Targeting autophagy during cancer therapy to improve clinical outcomes.

Pharmacology & therapeutics ·Vol. 131 ·No. 1 ·2011-07-00 ·Pages 130-41

Levy JM, Thorburn A

Abstract

Autophagy is a catabolic process that turns over long-lived proteins and organelles and contributes to cell and organism survival in times of stress. Current cancer therapies including chemotherapy and radiation are known to induce autophagy within tumor cells. This is therefore an attractive process to target during cancer therapy as there are safe, clinically available drugs known to both inhibit and stimulate autophagy. However, there are conflicting positive and negative effects of autophagy and no current consensus on how to manipulate autophagy to improve clinical outcomes. Careful and rigorous evaluation of autophagy with a focus on how to translate laboratory findings into relevant clinical therapies remains an important aspect of improving clinical outcomes in patients with malignant disease.

MeSH Terms
Animals Antineoplastic Agents/pharmacology,therapeutic use Autophagy/drug effects Humans Neoplasms/drug therapy,pathology Treatment Outcome
Chemicals
Antineoplastic Agents
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Levy Jean M Mulcahy
Department of Pediatrics, University of Colorado, 12801 E 17th Ave, RC-1 South, Rm 6400D, Mail Stop 8303, Aurora, CO 80045, USA.
Thorburn Andrew
References (188)
188 references, click to expand
  1. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.
    J Clin Invest. 2003 Dec;112(12):1809-20 PMID: 14638851
  2. Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis.
    J Clin Invest. 2008 Jan;118(1):79-88 PMID: 18097482
  3. Effect of a malaria suppression program on the incidence of African Burkitt's lymphoma.
    Am J Epidemiol. 1989 Apr;129(4):740-52 PMID: 2923122
  4. Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors.
    Genes Cancer. 2010 Jan;1(1):40-9 PMID: 20811583
  5. Profile of temsirolimus in the treatment of advanced renal cell carcinoma.
    Onco Targets Ther. 2010 Oct 05;3:191-6 PMID: 21049085
  6. Ambra1 regulates autophagy and development of the nervous system.
    Nature. 2007 Jun 28;447(7148):1121-5 PMID: 17589504
  7. CCI-779 plus cisplatin is highly effective against human melanoma in a SCID mouse xenotranplantation model.
    Pharmacology. 2007;79(4):207-13 PMID: 17377418
  8. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial.
    Ann Intern Med. 2006 Mar 7;144(5):337-43 PMID: 16520474
  9. Evolving strategies for overcoming resistance to HER2-directed therapy: targeting the PI3K/Akt/mTOR pathway.
    Clin Breast Cancer. 2010 Nov;10 Suppl 3:S72-8 PMID: 21115425
  10. Nelfinavir, a new anti-cancer drug with pleiotropic effects and many paths to autophagy.
    Autophagy. 2008 Jan;4(1):107-9 PMID: 18000394
  11. Autophagy and aging: lessons from progeria models.
    Adv Exp Med Biol. 2010;694:61-8 PMID: 20886757
  12. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes.
    Nat Cell Biol. 2004 Dec;6(12):1221-8 PMID: 15558033
  13. A genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers.
    Mol Cancer. 2010 Feb 25;9:44 PMID: 20184741
  14. Mechanism by which mammalian target of rapamycin inhibitors sensitize multiple myeloma cells to dexamethasone-induced apoptosis.
    Cancer Res. 2006 Feb 15;66(4):2305-13 PMID: 16489035
  15. Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype.
    Int J Cancer. 2008 Aug 15;123(4):760-8 PMID: 18512241
  16. Radiotracers for noninvasive molecular imaging of tumor cell death.
    Cancer Biother Radiopharm. 2010 Dec;25(6):615-28 PMID: 21204755
  17. Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells.
    Pancreatology. 2010;10(1):19-26 PMID: 20299819
  18. The aggresome pathway as a target for therapy in hematologic malignancies.
    Mol Genet Metab. 2008 Jul;94(3):283-6 PMID: 18472289
  19. Two ubiquitin-like conjugation systems essential for autophagy.
    Semin Cell Dev Biol. 2004 Apr;15(2):231-6 PMID: 15209383
  20. Autophagy and tumorigenesis.
    Semin Immunopathol. 2010 Dec;32(4):383-96 PMID: 20589500
  21. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains.
    Mol Cell Biol. 2009 May;29(10):2570-81 PMID: 19273585
  22. Decreased expression of Bax-interacting factor-1 (Bif-1) in invasive urinary bladder and gallbladder cancers.
    Pathology. 2008 Oct;40(6):553-7 PMID: 18752120
  23. The role of autophagy in cancer development and response to therapy.
    Nat Rev Cancer. 2005 Sep;5(9):726-34 PMID: 16148885
  24. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates.
    Mol Cell. 2009 Feb 27;33(4):517-27 PMID: 19250912
  25. Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy.
    Cancer Res. 2008 Mar 1;68(5):1485-94 PMID: 18316613
  26. The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma.
    Mol Cancer Res. 2010 Jul;8(7):1002-16 PMID: 20587533
  27. The mammalian target of rapamycin inhibitor RAD001 (everolimus) synergizes with chemotherapeutic agents, ionizing radiation and proteasome inhibitors in pre-B acute lymphocytic leukemia.
    Haematologica. 2011 Jan;96(1):69-77 PMID: 20952516
  28. Autophagy in the pathogenesis of disease.
    Cell. 2008 Jan 11;132(1):27-42 PMID: 18191218
  29. Everolimus - a new approach in the treatment of renal cell carcinoma.
    Cancer Manag Res. 2010 Mar 09;2:61-70 PMID: 21188097
  30. Elongation factor-2 kinase regulates autophagy in human glioblastoma cells.
    Cancer Res. 2006 Mar 15;66(6):3015-23 PMID: 16540650
  31. Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation.
    J Cell Mol Med. 2010 Oct;14(10):2448-59 PMID: 19583815
  32. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.
    Nat Cell Biol. 2011 Feb;13(2):132-41 PMID: 21258367
  33. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis.
    Genes Dev. 2007 Jul 1;21(13):1621-35 PMID: 17606641
  34. BNIP3 as a progression marker in primary human breast cancer; opposing functions in in situ versus invasive cancer.
    Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):467-74 PMID: 17255267
  35. DAP1, a novel substrate of mTOR, negatively regulates autophagy.
    Curr Biol. 2010 Jun 22;20(12):1093-8 PMID: 20537536
  36. Everolimus for advanced pancreatic neuroendocrine tumors.
    N Engl J Med. 2011 Feb 10;364(6):514-23 PMID: 21306238
  37. ADI, autophagy and apoptosis: metabolic stress as a therapeutic option for prostate cancer.
    Autophagy. 2009 May;5(4):567-8 PMID: 19276647
  38. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis.
    Cancer Cell. 2008 Apr;13(4):343-54 PMID: 18394557
  39. Targeted therapies and autophagy: new insights from chronic myeloid leukemia.
    Autophagy. 2009 Oct;5(7):1050-1 PMID: 19713759
  40. Acquired cisplatin resistance in human lung adenocarcinoma cells is associated with enhanced autophagy.
    Cancer Biother Radiopharm. 2010 Feb;25(1):75-80 PMID: 20187799
  41. Autophagy inhibition contributes to radiation sensitization of esophageal squamous carcinoma cells.
    Dis Esophagus. 2011 Aug;24(6):437-43 PMID: 21166739
  42. Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas.
    Cancer Res. 2010 Dec 15;70(24):10299-309 PMID: 21159649
  43. Decreased expression of tumour suppressor Bax-interacting factor-1 (Bif-1), a Bax activator, in gastric carcinomas.
    Pathology. 2006 Aug;38(4):312-5 PMID: 16916719
  44. Initiation of apoptosis and autophagy by photodynamic therapy.
    Autophagy. 2006 Oct-Dec;2(4):289-90 PMID: 16921269
  45. Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes.
    J Cell Biol. 1967 May;33(2):437-49 PMID: 4292315
  46. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer.
    Hum Pathol. 2010 Jan;41(1):107-12 PMID: 19762066
  47. Time course of vinblastine-induced autophagocytosis and changes in the endoplasmic reticulum in murine pancreatic acinar cells: a morphometric and biochemical study.
    Eur J Cell Biol. 1996 Dec;71(4):341-50 PMID: 8980904
  48. Autophagy: assays and artifacts.
    J Pathol. 2010 Jun;221(2):117-24 PMID: 20225337
  49. Autophagy suppresses tumor progression by limiting chromosomal instability.
    Genes Dev. 2007 Jun 1;21(11):1367-81 PMID: 17510285
  50. The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: beyond the usual suspects' review series.
    EMBO Rep. 2008 Sep;9(9):859-64 PMID: 18704115
  51. Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins.
    J Biol Chem. 2003 Sep 5;278(36):34568-81 PMID: 12813044
  52. p62 at the crossroads of autophagy, apoptosis, and cancer.
    Cell. 2009 Jun 12;137(6):1001-4 PMID: 19524504
  53. Autophagy thwarts muscle disease.
    Nat Med. 2010 Nov;16(11):1188-90 PMID: 21052066
  54. Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer.
    Breast Cancer Res Treat. 2011 Jan;125(2):447-55 PMID: 21107682
  55. Autophagy induction as an efficient strategy to eradicate tumors.
    Autophagy. 2008 Oct;4(7):923-5 PMID: 18716458
  56. Autophagy in cutaneous malignant melanoma.
    J Cutan Pathol. 2010 Feb;37(2):256-68 PMID: 19615007
  57. DNA mismatch repair initiates 6-thioguanine--induced autophagy through p53 activation in human tumor cells.
    Clin Cancer Res. 2007 Feb 15;13(4):1315-21 PMID: 17317843
  58. Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions.
    Hum Pathol. 2010 Apr;41(4):503-12 PMID: 20004946
  59. A natural BH3 mimetic induces autophagy in apoptosis-resistant prostate cancer via modulating Bcl-2-Beclin1 interaction at endoplasmic reticulum.
    Cell Death Differ. 2011 Jan;18(1):60-71 PMID: 20577262
  60. Autophagy-active beclin-1 correlates with favourable clinical outcome in non-Hodgkin lymphomas.
    Mod Pathol. 2010 Jul;23(7):937-50 PMID: 20473282
  61. Comprehensive analysis of expression pattern and promoter regulation of human autophagy-related genes.
    Apoptosis. 2009 Oct;14(10):1165-75 PMID: 19657746
  62. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis.
    Cancer Cell. 2006 Jul;10(1):51-64 PMID: 16843265
  63. Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways.
    Mol Pharmacol. 2007 Jul;72(1):29-39 PMID: 17395690
  64. Combined treatment with bortezomib plus bafilomycin A1 enhances the cytocidal effect and induces endoplasmic reticulum stress in U266 myeloma cells: crosstalk among proteasome, autophagy-lysosome and ER stress.
    Int J Oncol. 2011 Mar;38(3):643-54 PMID: 21174067
  65. The role of autophagy in tumour development and cancer therapy.
    Expert Rev Mol Med. 2009 Dec 02;11:e36 PMID: 19951459
  66. Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901.
    Acta Biochim Biophys Sin (Shanghai). 2008 Mar;40(3):194-201 PMID: 18330473
  67. Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma.
    Cancer. 2008 Nov 15;113(10):2665-70 PMID: 18833585
  68. Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome.
    Cancer Sci. 2008 Sep;99(9):1813-9 PMID: 18616529
  69. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation.
    Mol Biol Cell. 2011 Jan 15;22(2):165-78 PMID: 21119005
  70. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy.
    Science. 2011 Jan 28;331(6016):456-61 PMID: 21205641
  71. The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells.
    Int J Cancer. 2009 Aug 1;125(3):717-22 PMID: 19431142
  72. Autophagy: process and function.
    Genes Dev. 2007 Nov 15;21(22):2861-73 PMID: 18006683
  73. Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies.
    Mol Cancer Ther. 2008 Jun;7(6):1347-54 PMID: 18566209
  74. Autophagy in cellular growth control.
    FEBS Lett. 2010 Apr 2;584(7):1417-26 PMID: 20096689
  75. A small molecule inhibitor of inducible heat shock protein 70.
    Mol Cell. 2009 Oct 9;36(1):15-27 PMID: 19818706
  76. The role of autophagy in the treatment of pancreatic cancer with gemcitabine and ionizing radiation.
    Int J Oncol. 2010 Oct;37(4):821-8 PMID: 20811703
  77. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis.
    Genes Dev. 2011 Mar 1;25(5):460-70 PMID: 21317241
  78. mTOR signaling pathway is a target for the treatment of colorectal cancer.
    Ann Surg Oncol. 2009 Sep;16(9):2617-28 PMID: 19517193
  79. Loss of autophagy in the central nervous system causes neurodegeneration in mice.
    Nature. 2006 Jun 15;441(7095):880-4 PMID: 16625205
  80. Autophagic cell death: the story of a misnomer.
    Nat Rev Mol Cell Biol. 2008 Dec;9(12):1004-10 PMID: 18971948
  81. Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells.
    Cancer Res. 2006 Jun 1;66(11):5828-35 PMID: 16740722
  82. Radiation resistance of cancer stem cells: the 4 R's of radiobiology revisited.
    Stem Cells. 2010 Apr;28(4):639-48 PMID: 20135685
  83. Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells.
    Cancer Res. 2006 Oct 15;66(20):10040-7 PMID: 17047067
  84. Understanding the Warburg effect: the metabolic requirements of cell proliferation.
    Science. 2009 May 22;324(5930):1029-33 PMID: 19460998
  85. Induction of autophagy by drug-resistant esophageal cancer cells promotes their survival and recovery following treatment with chemotherapeutics.
    Autophagy. 2011 May;7(5):509-24 PMID: 21325880
  86. A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy.
    Cancer Cell. 2008 Jul 8;14(1):90-102 PMID: 18598947
  87. Autophagy in cancer: good, bad, or both?
    Cancer Res. 2006 Oct 1;66(19):9349-51 PMID: 17018585
  88. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.
    Autophagy. 2008 Feb;4(2):151-75 PMID: 18188003
  89. Inhibition of autophagy enhances anticancer effects of atorvastatin in digestive malignancies.
    Cancer Res. 2010 Oct 1;70(19):7699-709 PMID: 20876807
  90. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5.
    J Clin Invest. 2010 Jan;120(1):127-41 PMID: 20038797
  91. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.
    Nature. 2006 Jun 15;441(7095):885-9 PMID: 16625204
  92. Methods in mammalian autophagy research.
    Cell. 2010 Feb 5;140(3):313-26 PMID: 20144757
  93. The Beclin 1 network regulates autophagy and apoptosis.
    Cell Death Differ. 2011 Apr;18(4):571-80 PMID: 21311563
  94. Phase II study of everolimus (RAD001) in previously treated small cell lung cancer.
    Clin Cancer Res. 2010 Dec 1;16(23):5900-7 PMID: 21045083
  95. Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma.
    Leuk Res. 2009 Nov;33(11):1475-80 PMID: 19261329
  96. Exploring mammalian target of rapamycin (mTOR) inhibition for treatment of mantle cell lymphoma and other hematologic malignancies.
    Leuk Lymphoma. 2009 Dec;50(12):1916-30 PMID: 19757306
  97. Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3.
    J Biol Chem. 2007 Jun 22;282(25):18573-18583 PMID: 17442669
  98. mTOR signaling and drug development in cancer.
    Nat Rev Clin Oncol. 2010 Apr;7(4):209-19 PMID: 20234352
  99. Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer.
    Autophagy. 2010 Apr;6(3):322-9 PMID: 20224296
  100. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder--murine Pompe disease.
    Autophagy. 2010 Nov;6(8):1078-89 PMID: 20861693
  101. The prognostic role of Beclin 1 protein expression in high-grade gliomas.
    Autophagy. 2009 Oct;5(7):930-6 PMID: 19556884
  102. Small molecules and targeted therapies in distant metastatic disease.
    Ann Oncol. 2009 Aug;20 Suppl 6:vi35-40 PMID: 19617296
  103. Regulation of autophagy by ceramide-CD95-PERK signaling.
    Autophagy. 2008 Oct;4(7):929-31 PMID: 18719356
  104. Crosstalk between autophagy and apoptosis in the regulation of paclitaxel-induced cell death in v-Ha-ras-transformed fibroblasts.
    Mol Cell Biochem. 2011 Feb;348(1-2):61-8 PMID: 21069434
  105. HIF-1α-dependent autophagy protects HeLa cells from fenretinide (4-HPR)-induced apoptosis in hypoxia.
    Pharmacol Res. 2010 Nov;62(5):416-25 PMID: 20637870
  106. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice.
    J Clin Invest. 2008 Jun;118(6):2190-9 PMID: 18497889
  107. Arginine deprivation, autophagy, apoptosis (AAA) for the treatment of melanoma.
    Curr Mol Med. 2010 Jun;10(4):405-12 PMID: 20459375
  108. Autophagy and angiogenesis inhibition.
    Autophagy. 2007 Sep-Oct;3(5):512-5 PMID: 17643071
  109. Radiation-induced autophagy in normal and cancer cells: towards novel cytoprotection and radio-sensitization policies?
    Autophagy. 2009 May;5(4):442-50 PMID: 19164950
  110. Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia.
    Leukemia. 2011 May;25(5):781-91 PMID: 21331075
  111. Autophagy gets a brake: DAP1, a novel mTOR substrate, is activated to suppress the autophagic process.
    Autophagy. 2010 Nov;6(8):1179-80 PMID: 20818178
  112. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.
    Cell. 2005 Sep 23;122(6):927-39 PMID: 16179260
  113. Targeted therapy for the loss of von Hippel-Lindau in renal cell carcinoma: a novel molecule that induces autophagic cell death.
    Autophagy. 2008 Oct;4(7):944-6 PMID: 18769110
  114. Akt inhibitor shows anticancer and radiosensitizing effects in malignant glioma cells by inducing autophagy.
    Int J Oncol. 2007 Oct;31(4):753-60 PMID: 17786305
  115. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG.
    Nat Cell Biol. 2006 Jul;8(7):688-99 PMID: 16799551
  116. Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl-mediated drug resistance.
    Blood. 2007 Jul 1;110(1):313-22 PMID: 17363733
  117. Macroautophagy modulates cellular response to proteasome inhibitors in cancer therapy.
    Drug Resist Updat. 2010 Jun;13(3):87-92 PMID: 20462785
  118. Autophagy induction with RAD001 enhances chemosensitivity and radiosensitivity through Met inhibition in papillary thyroid cancer.
    Mol Cancer Res. 2010 Sep;8(9):1217-26 PMID: 20736296
  119. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial.
    J Clin Oncol. 2010 Jan 1;28(1):69-76 PMID: 19933912
  120. Chemopreventative potential of the cruciferous vegetable constituent phenethyl isothiocyanate in a mouse model of prostate cancer.
    J Natl Cancer Inst. 2011 Apr 6;103(7):571-84 PMID: 21330634
  121. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy.
    Clin Cancer Res. 2009 Feb 15;15(4):1126-32 PMID: 19228717
  122. Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells.
    Int J Oncol. 2005 May;26(5):1401-10 PMID: 15809734
  123. Induction of autophagic cell death in malignant glioma cells by arsenic trioxide.
    Cancer Res. 2003 May 1;63(9):2103-8 PMID: 12727826
  124. Targeting autophagy to fight hematopoietic malignancies.
    Cell Cycle. 2010 Sep 1;9(17):3470-8 PMID: 20703092
  125. DAPk protein family and cancer.
    Autophagy. 2006 Apr-Jun;2(2):74-9 PMID: 17139808
  126. Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs.
    Br J Cancer. 2008 Mar 11;98(5):923-30 PMID: 18319715
  127. Induction of autophagy by concanavalin A and its application in anti-tumor therapy.
    Autophagy. 2007 Jul-Aug;3(4):402-4 PMID: 17471013
  128. Induction of autophagy in temozolomide treated malignant gliomas.
    Neuropathology. 2011 Oct;31(5):486-93 PMID: 21269334
  129. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis.
    J Biol Chem. 2011 Feb 25;286(8):6602-13 PMID: 21148553
  130. Autophagy induction by Bcr-Abl-expressing cells facilitates their recovery from a targeted or nontargeted treatment.
    Am J Hematol. 2011 Jan;86(1):38-47 PMID: 21132731
  131. Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone.
    Breast Cancer Res. 2010;12 Suppl 2:S2 PMID: 21050423
  132. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.
    J Clin Invest. 2009 May;119(5):1359-72 PMID: 19425170
  133. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.
    Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15077-82 PMID: 14657337
  134. Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma.
    Clin Cancer Res. 2011 May 15;17(10):3478-89 PMID: 21325076
  135. Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells.
    J Clin Invest. 2009 May;119(5):1109-23 PMID: 19363292
  136. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex.
    Nat Cell Biol. 2009 Apr;11(4):468-76 PMID: 19270693
  137. Targeting cancer cells through autophagy for anticancer therapy.
    Curr Opin Cell Biol. 2010 Apr;22(2):246-51 PMID: 20056398
  138. Mechanism of autophagy to apoptosis switch triggered in prostate cancer cells by antitumor cytokine melanoma differentiation-associated gene 7/interleukin-24.
    Cancer Res. 2010 May 1;70(9):3667-76 PMID: 20406981
  139. Bcl-xL and UVRAG cause a monomer-dimer switch in Beclin1.
    J Biol Chem. 2008 Sep 19;283(38):26274-82 PMID: 18641390
  140. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG.
    Mol Biol Cell. 2008 Dec;19(12):5360-72 PMID: 18843052
  141. Beclin 1 over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumour hypoxia.
    Br J Cancer. 2010 Oct 12;103(8):1209-14 PMID: 20842118
  142. Light-chain 3A autophagic activity and prognostic significance in non-small cell lung carcinomas.
    Chest. 2011 Jul;140(1):127-134 PMID: 21148243
  143. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62.
    Cell Metab. 2006 Mar;3(3):211-22 PMID: 16517408
  144. Autophagy suppresses tumorigenesis through elimination of p62.
    Cell. 2009 Jun 12;137(6):1062-75 PMID: 19524509
  145. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment.
    Cell Cycle. 2010 Sep 1;9(17):3515-33 PMID: 20855962
  146. Assays to assess autophagy induction and fusion of autophagic vacuoles with a degradative compartment, using monodansylcadaverine (MDC) and DQ-BSA.
    Methods Enzymol. 2009;452:85-95 PMID: 19200877
  147. Effects of the mammalian target of rapamycin inhibitor CCI-779 used alone or with chemotherapy on human prostate cancer cells and xenografts.
    Cancer Res. 2005 Apr 1;65(7):2825-31 PMID: 15805283
  148. AKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001.
    Clin Cancer Res. 2009 Feb 15;15(4):1277-87 PMID: 19228731
  149. Vitamin D analog EB1089 triggers dramatic lysosomal changes and Beclin 1-mediated autophagic cell death.
    Cell Death Differ. 2005 Oct;12(10):1297-309 PMID: 15905882
  150. Autophagosome formation: core machinery and adaptations.
    Nat Cell Biol. 2007 Oct;9(10):1102-9 PMID: 17909521
  151. Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in ApcDelta716 mice.
    Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13544-9 PMID: 18768809
  152. Autophagy blockade enhances HDAC inhibitors' pro-apoptotic effects: potential implications for the treatment of a therapeutic-resistant malignancy.
    Autophagy. 2011 Apr;7(4):440-1 PMID: 21224727
  153. Induction of autophagy and inhibition of tumorigenesis by beclin 1.
    Nature. 1999 Dec 9;402(6762):672-6 PMID: 10604474
  154. Overexpression of the mammalian target of rapamycin: a novel biomarker for poor survival in resected early stage non-small cell lung cancer.
    J Thorac Oncol. 2010 Mar;5(3):314-9 PMID: 20093977
  155. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis.
    Nat Cell Biol. 2007 Oct;9(10):1142-51 PMID: 17891140
  156. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy.
    Mol Biol Cell. 2008 May;19(5):2092-100 PMID: 18321988
  157. Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition.
    Cancer Res. 2009 Jul 1;69(13):5467-74 PMID: 19549896
  158. A role for ubiquitin in selective autophagy.
    Mol Cell. 2009 May 15;34(3):259-69 PMID: 19450525
  159. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery.
    Mol Biol Cell. 2009 Apr;20(7):1992-2003 PMID: 19225151
  160. NF-kappaB inhibition sensitizes to starvation-induced cell death in high-risk myelodysplastic syndrome and acute myeloid leukemia.
    Oncogene. 2007 Jun 14;26(28):4071-83 PMID: 17213804
  161. CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium.
    Cancer. 2005 Sep 1;104(5):1045-8 PMID: 16007689
  162. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking.
    Nat Cell Biol. 2008 Jul;10(7):776-87 PMID: 18552835
  163. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors.
    Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18030-5 PMID: 15596714
  164. Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer.
    J Thorac Oncol. 2010 Oct;5(10):1637-43 PMID: 20808253
  165. Autophagy as the main means of cytotoxicity by glucocorticoids in hematological malignancies.
    Autophagy. 2009 Nov;5(8):1198-200 PMID: 19855186
  166. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents.
    J Cell Biol. 2008 Oct 6;183(1):101-16 PMID: 18838554
  167. Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model.
    Clin Cancer Res. 2009 Oct 1;15(19):6096-105 PMID: 19773376
  168. Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes.
    J Cell Biol. 2009 Sep 21;186(6):773-82 PMID: 19797076
  169. Autophagy induction by a natural ingredient of areca nut.
    Autophagy. 2008 Oct;4(7):967-8 PMID: 18758233
  170. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma.
    J Clin Invest. 2007 Feb;117(2):326-36 PMID: 17235397
  171. Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells.
    Gynecol Oncol. 2007 Apr;105(1):23-30 PMID: 17234261
  172. PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells.
    Cancer Res. 2010 Feb 1;70(3):1120-9 PMID: 20103619
  173. Autophagy regulates selective HMGB1 release in tumor cells that are destined to die.
    Cell Death Differ. 2009 Jan;16(1):175-83 PMID: 18846108
  174. Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells.
    Radiother Oncol. 2009 Sep;92(3):323-8 PMID: 19541381
  175. Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L.
    Cell Death Differ. 2008 Oct;15(10):1572-81 PMID: 18551130
  176. Cisplatin triggers atrophy of skeletal C2C12 myotubes via impairment of Akt signalling pathway and subsequent increment activity of proteasome and autophagy systems.
    Toxicol Appl Pharmacol. 2011 Feb 1;250(3):312-21 PMID: 21074548
  177. Role of autophagy in cancer.
    Nat Rev Cancer. 2007 Dec;7(12):961-7 PMID: 17972889
  178. Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo.
    Clin Cancer Res. 2007 Sep 1;13(17):5183-94 PMID: 17785575
  179. Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo.
    Mol Cancer. 2010 Mar 12;9:57 PMID: 20226010
  180. Parthenolide, an NF-κB inhibitor, suppresses tumor growth and enhances response to chemotherapy in gastric cancer.
    Cancer Genomics Proteomics. 2011 Jan-Feb;8(1):39-47 PMID: 21289336
  181. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis.
    N Engl J Med. 2010 Nov 4;363(19):1801-11 PMID: 21047224
  182. The mTOR pathway: a new target in cancer therapy.
    Curr Cancer Drug Targets. 2010 Aug;10(5):484-95 PMID: 20384580
  183. Inhibition of autophagosome formation by the benzoporphyrin derivative verteporfin.
    J Biol Chem. 2011 Mar 4;286(9):7290-300 PMID: 21193398
  184. TOR signaling in growth and metabolism.
    Cell. 2006 Feb 10;124(3):471-84 PMID: 16469695
  185. RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid.
    Prostate. 2008 Jun 1;68(8):861-71 PMID: 18361409
  186. Control of autophagy by oncogenes and tumor suppressor genes.
    Cell Death Differ. 2009 Jan;16(1):87-93 PMID: 18806760
  187. Concurrent and sequential administration of chemotherapy and the Mammalian target of rapamycin inhibitor temsirolimus in human cancer cells and xenografts.
    Clin Cancer Res. 2009 Sep 1;15(17):5389-95 PMID: 19706800
  188. Autophagy: from phenomenology to molecular understanding in less than a decade.
    Nat Rev Mol Cell Biol. 2007 Nov;8(11):931-7 PMID: 17712358
Article Info
Journal
Pharmacology & therapeutics
Abbr.
Pharmacol Ther
ISSN
1879-016X
DOI
10.1016/j.pharmthera.2011.03.009
Published
2011-07-00
Epub
2011-00-23
Pages
130-41
Language
English
Region
England
NLM ID
7905840
PMCID
PMC3539744
Subset
IM
Grants
NCI NIH HHS · R01 CA150925 · United States
NCI NIH HHS · CA111421 · United States
NCI NIH HHS · R01 CA150925-03 · United States
NCI NIH HHS · CA150925 · United States
NCI NIH HHS · R01 CA111421-08 · United States
NCI NIH HHS · R01 CA111421 · United States
External Links
PubMed source DOI: 10.1016/j.pharmthera.2011.03.009 PMC Full Text View journal details
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