Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review

Table 3 microRNAs and small interfering RNAs as therapeutics for colorectal cancer in clinical trials

Therapeutic name	Target gene/protein	Route of administration	Phase/status	Clinical trial identifier	Outcome
siRNA targeted therapeutics
ALN-VSP02	VEGF, KSP	Systemic	Phase I (2011)/terminated	NCT00882180	It was well-tolerated and had antitumor activity
		IV infusion	Phase I (2012)/completed	NCT01158079
Atu027	PKN3	Systemic	Phase I (2012)	NCT00938574	It was safe in patients with advanced solid tumors
		IV infusion	Phase I/II (2016)/completed	NCT01808638
CALAA-01	RRM 2	Systemic; IV infusion	Phase I (2013)/terminated	NCT00689065	It was well tolerated during the initial dose escalation portion of the phase Ia study
siRNA-EphA2-DOPC	EphA2	Systemic; IV infusion	Phase I 2015/active	NCT01591356	It was well tolerated at all doses tested in preclinical studies
TKM-PLK1 (TKM-080301)	PLK-1	Systemic; IV infusion	Phase I/II (2016)/completed	NCT02191878	It was tolerated and showed preliminary antitumor efficacy
DCR-MYC (DCRM1711)	MYC	Systemic	Phase I (2017)	NCT02110563	It was well tolerated and showed promising initial clinical and metabolic responses across various dose levels
		IV infusion	Phase Ib/2 (2016)/terminated	NCT02314052
NBF-006	GSTP	Systemic; IV infusion	Phase1 (2019)/active	NCT03819387	Significant tumor growth inhibition and overall survival benefit was observed
miRNA targeted therapeutics
MRX34	miR-34a mimic	IV infusion	Phase I/terminated-2016. Phase I-II/withdrawn-2016	NCT01829971	Unexpected severe immune-mediated toxicities observed
				NCT02862145

DCR-MYC: Lipid nanoparticle-formulated small inhibitory RNA; EphA2: Ephrin type-A receptor 2; GSTP: Glutathione S-transferase pi gene; IV: Intravenous; KSP: Kinesin spindle protein; miRNA: MicroRNA; PKN3: Protein kinase N3; PLK-1: Polo-like kinase 1; RRM2: Ribonucleotide reductase regulatory subunit M2; siRNA: Small interfering RNA; VEGF: Vascular endothelial growth factor.