TABLE 2

Summary of studies combining molecularly targeted agents with pharmacologic inhibition of autophagy

Therapeutic AgentModelAutophagy InhibitionResponseReference
ImatinibHuman glioma cell lines3-MethyladenineDecreased cytotoxicityShingu et al., 2009
Bafilomycin AIncreased cytotoxicity
ImatinibHuman Philadelphia chromosome positive CML cellsChloroquineIncreased cytotoxicityBellodi et al., 2009
HDACi/vorinostatHuman colon cancer cells and xenograftsChloroquineIncreased cytotoxicityCarew et al., 2010
Decreased growth
HDACi/panobinostatHuman triple negative breast cancer cells and xenograftsChloroquineIncreased cytotoxicityRao et al., 2012
Decreased tumor growth
HDACi/SAHAHuman CML cell lines and primary CML cellsChloroquineIncreased cytotoxicityCarew et al., 2007
HDACi/valproic acidHuman t(8;21) acute myeloid leukemia cellsChloroquineIncreased cytotoxicityTorgersen et al., 2013
HSP90i/DMAGHuman multiple myeloma cell lines3-MethyladenineIncreased cytotoxicityPalacios et al., 2010
ErlotinibHuman glioblastoma cell linesChloroquineIncreased cytotoxicityEimer et al., 2011
SorafenibHuman hepatocellular carcinoma cell lines and xenograftsChloroquineIncreased cytotoxicity and decreased tumor growthShi et al., 2011
3-Methyladenine
SorafenibHuman hepatocellular carcinoma cell lines and xenograftsChloroquineIncreased cytotoxicity and decreased tumor growthShimizu et al., 2012
SunitinibRat PC12 cellsAmmonium chlorideIncreased cytotoxicityIkeda et al., 2013
AKTi/AZD5363Human prostate cancer cell lines and xenograft3-MethyladenineIncreased cytotoxicity and decreased tumor growthLamoureux et al., 2013
Chloroquine
Bafilomycin A
METi/PHA665752 and EMD1214063Human gastric adenocarcinoma cell line3-MethyladenineIncreased cytotoxicityHumbert et al., 2013
VandetanibHuman glioblastoma cell lines and xenograft3-MethyladenineIncreased cytotoxicity and decreased tumor growthShen et al., 2013
Chloroquine
BevacizumabHuman hepatocellular carcinoma xenograftsChloroquineDecreased tumor growthGuo et al., 2013b
BortezomibHuman multiple myeloma cell line (U266)3-MethyladenineDecreased cytotoxicityKawaguchi et al., 2011
Bafilomycin AIncreased cytotoxicity
BortezomibHuman hepatocellular carcinoma cell lines and xenograftsChloroquineIncreased apoptosisHui et al., 2012
  • AKTi, AKT inhibitor; AZD5363, (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide; EMD1214063, 3-[1,6-dihydro-1-[[3-[5-[(1-methyl-4-piperidinyl)methoxy]-2-pyrimidinyl]phenyl]methyl]-6-oxo-3-pyridazinyl]benzonitrile; HDACi, histone deacetylase inhibitor; PHA665752, (2R)-1-[[5-[(Z)-[5-[[(2,6-dichlorophenyl)methyl]sulfonyl]-1,2-dihydro-2-oxo-3H-indol-3-ylidene]methyl]-2,4-dimethyl-1H-pyrrol-3-yl]carbonyl]-2-(1-pyrrolidinylmethyl)pyrrolidine.