ORLANDO, Florida (Reuters Health) - Cancer researchers today unveiled a small molecule, CX-3543, that significantly curbs the growth of a variety of tumors in animals by suppressing the action of the proto-oncogene, c-Myc.
“CX-3543 has been a very impressive compound in animal tumor models and we are looking forward to moving it into clinical development,” Dr. William G. Rice, from Cylene Pharmaceuticals in San Diego, California said during a press briefing today at the 95th annual meeting of the American Association for Cancer Research.
The oncogene c-Myc is highly prevalent in multiple tumor types and one that until now had been an “undruggable,” target, Dr. Rice and colleagues explain in a meeting abstract.
CX-3543 suppresses c-Myc activity by binding to the c-Myc quadruplex, four-stranded DNA secondary structures that regulate transcription of specific oncogenes including c-Myc. CX-3543 also suppresses expression of the angiogenesis promoter VEGF.
In a colorectal cancer xenograft model, CX-3543 produced an 85% reduction in c-Myc mRNA levels and up to 85% reduction in tumor growth, depending on the dose and schedule.
“In refractory prostate cancer xenografts, we saw essentially complete reduction in tumor growth and when we compared CX-3543 to Taxol we saw at least equivalent if not better inhibition,” Dr. Rice reported. “Also, in a very-difficult-to-treat pancreatic cancer model, we saw anywhere from 50% to 90% reductions in tumor growth depending on the dose of CX-3543. All of these tumors are largely driven by high levels of c-Myc.
Dr. Geoff M. Wahl, from The Salk Institute in La Jolla, California and program chair for this year’s AACR meeting said CX-3543 represents “one exciting advance in taking cancer-specific gene alterations and targeting them. This is a new direction in which cancer therapy must go in the future.”
MeSH Headings:Animal Diseases: Colonic Diseases: Digestive System Neoplasms: Disease Models, Animal: DNA-Binding Proteins: Gastrointestinal Neoplasms: Growth Inhibitors: Intestinal Neoplasms: Neoplasms: Neoplasms by Site: Nuclear Proteins: Proto-Oncogene Proteins: Colorectal Neoplasms: Drugs, Investigational: Genes, myc: Proto-Oncogene Proteins c-myc: Angiogenesis Inhibitors: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
