Toll-like receptor signaling in colorectal cancer: Carcinogenesis to cancer therapy

Table 1 Toll-like receptor functions in disease and cancer

TLR	Disease	Function
TLRs	Autoimmune disease	Microbe-host interactions and innate immunity
TLRs	Infectious disease	Activating canonical and non-canonical pathways of inflammation
TLRs	Cancer (CRC, HCC, etc)	Carcinogenesis
TLRs	Allergic diseases	Primary sensors of PAMPs, DAMPs and stress signals associated with allergen exposure
TLRs	Tuberculosis	Recognition of Mycobacterium tuberculosis
TLRs	Systemic inflammatory response syndrome	Development of syndrome
TLR2/TLR4	Atherosclerosis	Development of disease
TLR4	NEC	Development of intestinal barrier failure
TLR4	Alcohol-induced liver injury	Activation of Kupffer cells
TLR9	NASH	Development of disease
TLR9	Cancer	Angiogenesis

TLR: Toll-like receptor; CRC: Colorectal cancer; HCC: Hepatocellular carcinoma; PAMPs: Pathogen-associated molecular patterns; DAMPs: Danger associated molecular patterns; NEC: Necrotizing enterocolitis; NASH: Non-alcoholic steatohepatitis.

Table 2 Toll-like receptors role in colorectal cancer

TLR	Carcinogenesis	Prognosis	Treatment
TLR2	Controversial role in mouse model; protective against development of CRC in colitis	Associated with survival after diagnosis of colon cancer	HMGB1, S100A9
TLR4	Oncogenic effects in vitro and in vivo	Poor progression	HMGB1, S100A9, MPLA
TLR9	Remain unclear; possible protection against malignant transformation in colorectal mucosa		CpG-ODN

CRC: Colorectal cancer; TLR: Toll Like receptor.

Table 3 Summary of therapy in colorectal cancer

Compound	Target (agonist)	Indications	Drug class or trade	Clinical phase
BCG[10,71,72]	TLR2/4	CRC	Synthetic ssRNA	Phase I
MPL[10,72]	TLR4	CRC	Synthetic ssRNA	Phase I
CBLB502[1,23,71]	TLR5	Colon cancer	Flagellin	Phase I
Imiquimod (Aldara)[10,71,72]	TLR7	CRC	Small molecule ssRNA	Phase I/II/III
IMO2055[1,10]	TLR9	CRC	CpG oligonucleotide	Phase I/II
MGN1703[16]	TLR9	CRC	dSLIM	Phase II