Sustained inhibition of cMET-VEGFR2 signaling using liposome-mediated delivery increases efficacy and reduces toxicity in kidney cancer

We report the development of a multi-receptor tyrosine kinase inhibitor liposomes for increasing anti-tumor efficacy, reducing toxicity and overcoming resistance in renal cell carcinoma (RCC). We have shown that the liposomes targeting multiple tyrosine-kinase pathways such as cMet, VEGFR, RET and Tie-2 simultaneously resulted in increased efficacy in vitro in multiple RCC cell lines and sustained inhibition of multiple feedback signaling pathways in vitro and in vivo thereby overcoming resistance. Preferential accumulation of drug was observed in the tumor as compared to other organs when injected as liposomes which resulted in lower systemic toxicities.108