Table 1.

Effective combinations of trifluorothymidine or TPI (in vitro) or TAS-102 (in vivo) with conventional chemotherapy targeted against DNA and novel therapeutics targeting protein kinases.

Drug	Combination drug	Model system	In vitro/in vivo	Outcome	Postulated mechanism	Reference
Trifluorothymidine	Oxaliplatin	Colon cancer	In vitro	Synergistic	Increased DNA adducts	Temmink et al. [2007d]
TAS-102	Oxaliplatin	Colon and gastric cancer	In vivo	Synergistic		Nukatsuka et al. [2015a]
Trifluorothymidine	Irinotecan	Colon cancer	In vitro	Synergistic	Increased DNA damage and apoptosis	Temmink et al. [2007c]
TAS-102	Irinotecan	Colon and gastric cancer	In vivo			Nukatsuka et al. [2015b]
Trifluorothymidine	Docetaxel	Colon cancer	In vitro	Synergistic	Cell-cycle arrest; cell kill	Bijnsdorp et al. [2008]
Trifluorothymidine	Antifolates	Colon cancer	In vitro	Synergistic/additive	DNA damage	Temmink et al. [2006b]
TPI	Rapamycin	Colon cancer	In vitro	Synergistic	TPI prevents autophagy	Bijnsdorp and Peters [2011]
Trifluorothymidine	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	Lung cancer	In vitro	Synergistic	Induction caspase pathway	Azijli et al. [2014]
Trifluorothymidine	Radiation	Colon cancer	In vitro	Synergistic	Decreased repair DNA damage	El-Naggar et al. [2014]
TAS-102	Radiation	Colon cancer	In vivo	Sensitization	Angiogenesis and decreased DNA repair	Miyatani et al. [2012]
Trifluorothymidine	Erlotinib	Colon cancer	In vitro	Synergistic	S-phase arrest; no DNA repair	Bijnsdorp et al. [2010b]
TAS-102	Cetuximab, panitumumab	Colon cancer	In vivo			Tsukihara et al. [2015]
TAS-102	Bevacizumab	Colon cancer	In vivo		Increased TFT-phosphates	Tsukihara et al. [2015]