Table 3.

The Distinctive Properties of AIKs and PIKs

Anti-Inflammatory Kinases (AIKs)	Pro-Inflammatory Kinases (PIKs)
EGFR, VEGFR, PEGFR, VEGFR, BCR-ABL1, ALK, KIT, DDR, BRAF (a partial list)	JAK1, JAK2, JAK3, TYK2, SYK
“high Treg” diseases	“low Treg” diseases
Most solid cancers, CLL, ALL, MCL, CML, AMD	Autoimmune diseases, MPNs
Direct pro-tumor effect + anti-inflammatory effect	Direct tissue damage + pro-inflammatory effect
Diseases driven by AIKs are associated with “high Treg” pathogens	Diseases driven by PIKs are associated with “low Treg” pathogens
“High Treg” pathogens activate AIKs	“Low Treg” pathogens activate PIKs
	“High Treg” pathogens inhibit PIKs
Pathogens that activate both AIKs and PIKs induce both “high Treg” cancers and autoimmune diseases	Pathogens that activate both AIKs and PIKs induce both “high Treg” cancers and autoimmune diseases
Alcohol activate the Src family of kinases (AIKs)	Alcohol activate the Src family of kinases (AIKs)
Alcohol consumption increases the risk of “high Treg” cancers	Alcohol consumption decreases the risk of some autoimmune diseases
JAK1 loss-of-function mutations are frequent in diseases with high tumor-infiltrating Tregs	JAK1 gain-of-function mutations are frequent in “low Treg” diseases
AIK inhibitors are approved for the treatment of “high Treg” cancers but not for the treatment “low Treg” diseases (such as autoimmune diseases and MPNs).	PIK inhibitors (JAK inhibitors) are approved for the treatment of “low Treg” diseases (autoimmune diseases and MPNs) but not for the treatment “high Treg” cancers.
Can AIK inhibitors treat “low Treg” diseases (autoimmune diseases for example)?	Can PIK inhibitors (JAK inhibitors) treat “high Treg” cancers?