Mutant Kras is a druggable target for pancreatic cancer
ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery […]
Multistep effective drug distribution within solid tumors
Amotz Shemi, Elina Zorde Khvalevsky, Rachel Malka Gabai, Abraham Domb, Yechezkel Barenholz, Oncotarget , Sep 22, 2015Abstract: The distribution of drugs within solid tumors presents a long-standing barrier for efficient cancer therapies. Tumors are highly resistant to diffusion, and the lack of blood and lymphatic flows suppresses convection.Prolonged, continuous intratumoral drug delivery from a miniature drug source offers an alternative to both […]
Preclinical safety evaluation in rats of a polymeric matrix containing an sirna drug used as a local and prolonged delivery system for pancreatic cancer therapy
Ramot Y, Rotkopf S, Gabai RM, Khvalevsky EZ, Muravnik S, Marzoli GA, Domb AJ, Shemi A, Nyska A.Abstract: Conventional chemotherapy treatments for pancreatic cancer are mainly palliative. RNA interference (RNAi)-based drugs present the potential for a new targeted treatment. LOcal Drug EluteR (LODERTM) is a novel biodegradable polymeric matrix that shields drugs against enzymatic degradation […]
Pancreas adenocarcinoma novel therapeutics
Benjamin A. Krantz, Kenneth H. Yu, Eileen M. O’Reilly.Chinese Clinical Oncology. 2017.“Targeting RAS by inhibiting translation using small-interfering RNAs is a novel strategy to decrease RAS activity. siRNA against the G12D mutantRAS RNA by local prolonged delivery, KRAS-LODER (Local Drug EluteR), has demonstrated decreased growth of human pancreatic tumor cells in vivo and prolonged mouse survival. […]
The race of 10 synthetic rnai based drugs to the pharmaceutical market
Ricardo Titze-de-Almeida, Catherine David & Simoneide Souza Titze-de-Almeida. Pharmaceutical Research. 2017.“KRAS-LODER made KRAS a druggable anticancer target. New drugs also targeting this oncogene are now in test and may represent future competitors of KRAS-LODER. KRAS-LODER is the only RNAi-based drug that provides a sustained release of siRNA into the tumor region thanks to a well-known biodegradable […]