Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy

Table 1

Autophagy modulators in preclinical studies and clinical trials for cancer therapy.

	Cancer type	Autophagy modulators	Mode of action	Model tested/clinical trial phase	Reference of study/trial reference at ClinicalTrials.gov
Pancreas cancers	PDAC	CQ	Lysosomal inhibitor	Pancreatic cancer xenografts and mouse models	[100]
	PDAC	HCQ	Lysosomal inhibitor	PDAC mouse model	[101]
	Stage IIb or III pancreatic adenocarcinoma	HCQ + gemcitabine	Lysosomal inhibitor + inhibitor of DNA synthesis	Phase I/II	NCT01128296
	Advanced and metastatic pancreatic adenocarcinoma	HCQ + gemcitabine/abraxane	Lysosomal inhibitor + inhibitor of DNA synthesis/cell division inhibitor	Phase I/II	NCT01506973
	Metastatic pancreatic adenocarcinoma	HCQ	Lysosomal inhibitor	Phase II	[102]/NCT01273805
	Resectable pancreatic cancer	HCQ + capecitabine	Lysosomal inhibitor + inhibitor of DNA synthesis	Phase II	NCT01494155
	Resectable pancreatic adenocarcinoma	HCQ + gemcitabine + nab-paclitaxel	Lysosomal inhibitor + inhibitor of DNA synthesis + cell division inhibitor	Phase II	NCT01978184
	Resectable pancreatic adenocarcinoma	Gemcitabine, nab-paclitaxel, HCQ +/− avelumab	Inhibitor of DNA synthesis + cell division inhibitor + lysosomal inhibitor +/− T-cell activator	Phase II	NCT03344172
Breast cancers	Metastatic breast cancer	HCQ + ixabepilone	Lysosomal inhibitor + cell division inhibitor	Phase I/II	NCT00765765
	Advanced or metastatic breast cancer	CQ + taxane	Lysosomal inhibitor + cell division inhibitor	Phase II	NCT01446016
	Ductal carcinoma in situ	CQ	Lysosomal inhibitor	Phase I/II	NCT01023477
	Primary invasive breast cancer	CQ	Lysosomal inhibitor	Phase II	NCT02333890
Hepatocellular cancers	HCC after liver transplantation	Sirolimus	mTORC1 inhibitor	Phase II/III	[125]/NCT00328770
	Advanced HCC	Sirolimus	mTORC1 inhibitor	Phase II	[126]/NCT01079767
	HCC	RAD001 (everolimus)	mTORC1 inhibitor	Xenograft models of human HCC	[127]
	Advanced HCC	RAD001 (everolimus)	mTORC1 inhibitor	Phase III	[128]/NCT01035229
	HCC	RAD001 (everolimus) + BEZ235	mTORC1 inhibitor + new-generation mTORC1 (mTORC2) inhibitor	Human HCC cell lines and HCC mouse model	[130]
	HCC	RAD001 (everolimus) + SBI-0206965	mTORC1 inhibitor + ULK1 inhibitor	Different human cancer cell lines	[129]
	Advanced HCC	Sorafenib	mTORC1 inhibitor	Phase III	[132]/NCT00105443
	Advanced HCC	Sorafenib	mTORC1 inhibitor	Phase III	[133]/NCT00492752
	HCC	Sorafenib and SC-59	mTORC1 inhibitors	Human HCC cell lines and HCC mouse models	[134]
	HCC	Sorafenib + pemetrexed	mTORC1 inhibitors	Different human cancer cell lines and mouse models	[135]
	Advanced HCC	Sorafenib + HCQ	mTORC1 inhibitor + lysosomal inhibitor	Phase II	NCT03037437
	Unresectable HCC	HCQ	Lysosomal inhibitor	Phase I/II	NCT02013778
Colorectal cancers	CRC	CQ + 5-FU	Lysosomal inhibitor + inhibitor of DNA synthesis	CRC cell lines	[142, 150]
	CRC	3-MA + 5-FU	Lysosomal inhibitor + inhibitor of DNA synthesis	CRC cell lines	[77]
	CRC	CQ + 5-FU	Lysosomal inhibitor + inhibitor of DNA synthesis	CRC cell lines + mouse models	[150]
	CRC	CQ + vorinostat	Lysosomal inhibitor + histone deacetylase inhibitor	CRC cell lines + mouse models	[151]
	CRC	CQ + bortezomib	Lysosomal inhibitor + proteasomal inhibitor	CRC cell lines + mouse models	[152]
Lung cancers	NSCLC	CQ + erlotinib	Lysosomal inhibitor + EGFR-TKI	NSCLC cell lines	[157]
	NSCLC	CQ + gefitinib + cisplatin	Lysosomal inhibitor + EGFR-TKI + inhibitor of DNA synthesis	NSCLC cell lines	[158]
	NSCLC	CQ + SIRPαD1-Fc	Lysosomal inhibitor + cell division inhibitor	NSCLC cell lines	[161]
	Advanced NSCLC	HCQ	Lysosomal inhibitor	Phase I	[162]/NCT01026844
	Advanced NSCLC	HCQ + erlotinib	Lysosomal inhibitor + EGFR-TKI	Phase I	[162]/NCT01026844
	Advanced NSCLC	HCQ + erlotinib	Lysosomal inhibitor + EGFR-TKI	Phase II	NCT00977470

PDAC: pancreatic ductal adenocarcinoma; HCC: hepatocellular carcinoma; CRC: colorectal cancer; NSCLC: non-small cell lung cancer; CQ: chloroquine; HCQ: hydroxychloroquine; 5-FU: 5-fluorouracil; 3-MA: 3-methyladenine; SIRPαD1-Fc: signal regulatory protein α D1-Fc; mTORC: mammalian target of rapamycin complex; ULK1: Unc-51-like kinase 1; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitor.