Table 6.

Mechanisms of chemoresistance type 6 (MOC-6) to drugs used in the treatment of GAC.

Factor	Feature	Drugs Affected	Consequences	Ref.
Hypoxia
HIF-1α	Up-regulation	5-FU, Platinum derivatives	Apoptosis inhibition	[156,157,158,159]
	Up-regulation	5-FU	Relapse after treatment	[161]
STC1	Up-regulation	Cisplatin	Apoptosis inhibition	[162]
Immune system and inflammation
APRIL	Increased production	Cisplatin	Apoptosis inhibition	[164]
CCL2	Increased production	Cisplatin	Apoptosis inhibition	[165]
Fn14	Increased production	5-FU	Apoptosis inhibition	[166]
IL-6	Increased production	5-FU	Poor response	[167]
IL-8	Increased production	Platinum derivatives	ABCB1 overexpression and Apoptosis inhibition	[14,168]
IL-11	Increased production	Several drugs	Apoptosis inhibition	[169]
IL-33	Increased production	Platinum derivatives	Apoptosis inhibition	[170]
NR4A2	High expression	5-FU	Apoptosis inhibition and worse survival rates	[163]
Others
ATG-5	High expression	5-FU, Cisplatin, Epirubicin	Poor survival	[171]
Glycemia	Low levels	5-FU	Metabolic reprogramming and activation of survival	[172]
Glycolysis enzymes	Up-regulation	5-FU	Metabolic reprogramming	[173]
lncRNA HCP5	Production	5-FU, Oxaliplatin	Metabolic reprogramming	[174]
MSC-Exosomes	Production	5-FU	Activation of other MOCs	[175]
TAM-Exosomes	miR-21a-5p transfer	Cisplatin	Apoptosis inhibition	[176]

5-FU, 5-fluorouracil; MOCs, mechanisms of chemoresistance.