Authors
Josep Tabernero, Geoffrey I Shapiro, Patricia M LoRusso, Andres Cervantes, Gary K Schwartz, Glen J Weiss, Luis Paz-Ares, Daniel C Cho, Jeffrey R Infante, Maria Alsina, Mrinal M Gounder, Rick Falzone, Jamie Harrop, Amy C Seila White, Iva Toudjarska, David Bumcrot, Rachel E Meyers, Gregory Hinkle, Nenad Svrzikapa, Renta M Hutabarat, Valerie A Clausen, Jeffrey Cehelsky, Saraswathy V Nochur, Christina Gamba-Vitalo, Akshay K Vaishnaw, Dinah WY Sah, Jared A Gollob, Howard A Burris III
Publication date
2013/4/1
Journal
Cancer discovery
Volume
3
Issue
4
Pages
406-417
Publisher
American Association for Cancer Research
Description
RNA interference (RNAi) is a potent and specific mechanism for regulating gene expression. Harnessing RNAi to silence genes involved in disease holds promise for the development of a new class of therapeutics. Delivery is key to realizing the potential of RNAi, and lipid nanoparticles (LNP) have proved effective in delivery of siRNAs to the liver and to tumors in animals. To examine the activity and safety of LNP-formulated siRNAs in humans, we initiated a trial of ALN-VSP, an LNP formulation of siRNAs targeting VEGF and kinesin spindle protein (KSP), in patients with cancer. Here, we show detection of drug in tumor biopsies, siRNA-mediated mRNA cleavage in the liver, pharmacodynamics suggestive of target downregulation, and antitumor activity, including complete regression of liver metastases in endometrial cancer. In addition, we show that biweekly intravenous administration of ALN-VSP was safe …
Scholar articles
J Tabernero, GI Shapiro, PM LoRusso, A Cervantes… - Cancer discovery, 2013