Regulation of colon cancer recurrence and development of therapeutic strategies

Table 1 Drugs currently under clinical investigation for the treatment of recurrent colon cancer¹

Trail	Drug(s)/agent(s)	Target	Mechanism	Prior experiments
Phase II	R935788/fostamatanib disodium	Kinase inhibitor	Interference with cell communication thereby inhibiting tumor growth	On NCI-60 cell lines
Phase II	Anti ESO-TCR engineered lymphocytes + IL-2 + ALVAC ESO-1 vaccine		Tumor regression secondary to secretion of IFN-gamma by the anti-ESO-TCR induced cells + development of immunity from ALVAC ESO-1 vaccine	On HLA-A2 and ESO double positive tumors
Phase II	Bay 43-9006 + cetuximab	Kinase inhibitor	Inhibition of Raf pathway and VEGFR-2 by Bay 43-9006 + Ras and EGFR inhibition by cetuximab	With cetuximab
Phase II	MSLS + CRS + HIPEC		CRC + HIPEC for overall improvement in survival and MSLS to detect peritoneal carcinomatosis early on	Study results with increased survival of 48-63 mo from CRC + HIPEC when compared to 5-16 mo from chemotherapy alone in metastatic CRC patients
Phase II	Autologous CD8+ enriched young TIL + IL-2		TIL mediated regression of tumor bulk	Evidence of response rates in Metastatic melanoma upon infusion of young CD8+ enriched TIL + IL-2 after a lymphocyte depleting chemo preparative therapy.
Phase II	Echinomycin	Intercalating agent	Anti tumor properties from inhibition of stem cell RNA and DNA synthesis by intercalating into both strands of DNA thereby preventing synthesis	Evidence from trials of southwest oncology group for compounds with ability to modify fluropyrimidine activity
Phase III	Optimized chemotherapy + avastin strategy + tarceva
Phase II	Bortezomib

¹From http://www.cancer.gov. MSLS: Mandatory second look surgery; IL: Interleukin; CRS: Cytoreductive surgery; HIPEC: Hyperthermic intraperitoneal chemotherapy; TIL: Tumor infiltrating lymphocytes; CRC: Colorectal cancer.

Table 2 Major natural compounds targeting Wnt/β-catenin pathway undergoing clinical trials for the treatment of colon cancer

Category	Compound	Target	Mechanism	Clinical trials
				identification No.
Vitamins	Retinoids/vitamin-A	Beta-catenin	Compete with TCFs, production of inhibitory protein-disabled-2	NCT00270647, NCT00712647
	Vitamin-D	Beta-catenin	Production of inhibitory proteins-dickkopf-1 and 4	NCT00208793, NCT00870961, NCT01198548, NCT00399607, NCT01150877, NCT00585637
	Vitamin-E	Unknown	Unknown	NCT00706121, NCT00270647
	Pyridoxine	Unknown	Unknown	NCT00559858
Polyphenols	Quercetin	Wnt/beta-catenin	Unknown	NCT00003365
	Epigallocatechin-3-gallate from green tea	Wnt/beta-catenin	Plieotropic	NCT01239095, NCT00718094
	Curcumin	Wnt/beta-catenin	Plieotropic	NCT00365209, NCT00295035, NCT00027495, NCT00973869, NCT00745134, NCT00118989, NCT00927485, NCT00641147
	Resveratrol	Wnt/beta-catenin	Unknown	NCT00256334, NCT00578396, NCT00433576, NCT00920803
	Dictyostelium discoidem	Wnt/beta-catenin	Activation of GSK-3beta by differentiation inducing factors-1,3	No current trails
Lipids	Omega 3 fatty acids and n-3 polyunsaturated fatty acids	Mitochondrial membrane of tumor cells	Enhanced reactive oxygen species generation and decreased cell anti-oxidant capacity leading to apoptosis in tumor cells	NCT01127867, NCT00145015, NCT01218841, NCT00432913, NCT00488904, NCT00168987, NCT00510692, NCT01070355, NCT01048463

ID numbers source: clinicaltrails.gov.