TABLE 3.

Summary of studies evaluating pan-HDAC inhibitors in combination with other antitumor drugs.

HDACis	Drug combination	Class of drug combination	Cancer types	Effects	Clinical status	References and trial identifier
Abexinostat	Pazopanib	Tyrosine kinase pathway inhibitors	Advanced solid tumor malignancies	Blockade VEGF pathway.	Phase I	Aggarwal et al., 2017; NCT01543763
Belinostat	Doxorubicin	Alkylant agent	Soft tissue sarcoma	Well-tolerated combination. Response rate was moderate.	Phase I/II	Vitfell-Rasmussen et al., 2016; NCT00878800
	Paclitaxel and carboplatin	Alkylant agent	Carcinoma of unknown primary site	No effects	Phase II	Hainsworth et al., 2015; NCT00873119
	Cisplatin and etoposide	Alkylant agent	Small cell lung cancer	The combination is safe.	Phase I	Balasubramaniam et al., 2018; NCT00926640
	Anti-CTLA-4 and anti-PD-1 antibodies	Immunotherapy	Hepatocellular carcinoma	Improve antitumor activity in vivo.	Preclinical	Llopiz et al., 2019
Butyrate	5-Azacytidine	Epigenetic drugs	Breast cancer	Blockade mammary tumorigenesis and reduction tumorosphere-forming.	Preclinical	Pathania et al., 2016
Givinostat	Doxorubicin	Alkylant agent	Different sarcomas	Cell growth reduction. Apoptosis increase. Tumor growth inhibition.	Preclinical	Di Martile et al., 2018
OKI-179	Anti-PD1 antibody	Immunotherapy	Lymphoma	HDACis sensitize lymphomas to PD1-blokage by enhance tumor immunogenicity.	Preclinical	Wang et al., 2019
Panobinostat	Bortezomib and dexamethasone	Proteasome inhibitor	Multiple myeloma	Increase in progression free survival.	Phase III	Richardson et al., 2016; NCT01023308
	Carfilzomib	Proteasome inhibitor	Multiple myeloma	Combination safe and effective.	Phase I	Kaufman et al., 2019; NCT01549431
	Radiation	Radiotherapy	Bladder cancer	Increase growth delay in tumor xenografts.	Preclinical	Groselj et al., 2018
Quisinostat	Flavopiridol	Tyrosine kinase pathway inhibitors	Cutaneous and uveal metastatic melanoma	Cell proliferation reduction. Cell cycle arrest and apoptosis inhibition. Tumor growth inhibition.	Preclinical	Heijkants et al., 2018
	Flavopiridol	Tyrosine kinase pathway inhibitors	Cutaneous melanoma	Tumor growth inhibition and regression.	Preclinical	Heijkants et al., 2018
Valproic acid (VPA)	Cisplatin	Alkylant agent	Lung cancer	Induction of apoptosis and cell cycle perturbation.	Preclinical	Gumbarewicz et al., 2016
SAHA	Cisplatin	Alkylant agent	Larynx cancer	Cell proliferation suppression. Induce cell cycle arrest and apoptosis.	Preclinical	Grabarska et al., 2017
	Cisplatin	Alkylant agent	Lung cancer	Induction of apoptosis and cell cycle perturbation	Preclinical	Gumbarewicz et al., 2016
	Doxorubicin	Alkylant agent	Lymphoma	No study results posted	Phase I/II	NCT00785798
	Rituximab-CHOP	Alkylant agent	Diffuse large b-cell lymphoma	Increased toxicity	Phase I/II	Persky et al., 2018; NCT00972478
	Bortezomib	Proteasome inhibitor	Cervical cancer	Potent anti-tumor effects and lead to tumor-specific immunity.	Preclinical	Huang et al., 2015
	Carfilzomib	Proteasome inhibitor	B-cell lymphomas	No effects or modest effects	Phase I	Holkova et al., 2016; NCT01276717
	Sapanisertib	Tyrosine kinase pathway inhibitors	Lung cancer	Oxidative stress	Preclinical	Malone et al., 2017
	Ridaforolimus	Tyrosine kinase pathway inhibitors	Renal carcinoma and other solid tumors	No molecular effects	Phase I	Zibelman et al., 2015
	AZD1775	Tyrosine kinase pathway inhibitors	Head and neck squamous cell carcinoma	WEE1 inhibition leads to mitotic disfunction and increase DNA damage and apoptosis.	Preclinical	Tanaka et al., 2017
	131I-Metaiodobenzylguanidine	Radiotherapy	Neuroblastoma	Good outcome	Phase I	DuBois et al., 2015; NCT01019850
	Chemoradiation therapy	Radiotherapy	Head and neck squamous carcinoma	Combination safe and effective.	Phase I	Teknos et al., 2019
	Radiation	Radiotherapy	Pancreatic cancer	Induction of apoptotic response.	Preclinical	Moertl et al., 2019
	HCI-2509	Epigenetic drugs	Ewing sarcoma	Cell cycle arrest. Induction of apoptosis. Migratory capacity inhibition.	Preclinical	Garcia-Dominguez et al., 2018
	Decitabine	Epigenetic drugs	Acute myeloid leukemia	Stabilization of marrow disease.	Clinical trial	Glasser et al., 2017
	Ex917	Epigenetic drugs	Rhabdomyosarcoma	Cell death induction.	Preclinical	Haydn et al., 2017
	Pembrolizumab	Immunotherapy	Non-small lung cancer	Preliminary anti-tumor activity.	Preclinical	Gray et al., 2019
	Anti-CTLA-4 and anti-PD-1 antibodies	Immunotherapy	Breast cancer	Reduction tumor growth and increased survival.	Preclinical	Terranova-Barberio et al., 2017b