Cyclotide-based therapy for targeting RAS/RAF in pancreatic cancer
Innovative cyclotide-based therapeutic targeting various KRAS mutants in pancreatic cancer, demonstrating strong metabolic stability and efficacy in preclinical models.
Overview
The University of South California presents a groundbreaking cyclotide-based therapeutic approach for targeting the RAS/RAF pathway in pancreatic cancer. This approach employs a novel cyclotide, MCo-RR7-cTAT, which effectively antagonizes interactions between the RAS-binding domain of RAF and various KRAS mutants, including G12D, G12V, and G12C. This innovation addresses the urgent need for alternative treatments for KRAS-driven cancers, particularly pancreatic ductal adenocarcinoma (PDAC), by offering a solution with considerable metabolic stability and efficacy.
Technical specifications
Key features:
- Cyclotide Design: MCo-RR7-cTAT is engineered to disrupt the interaction between RAF isoforms (aRaf, bRAF, cRAF) and KRAS, including wild-type and mutant forms (G12D, G12V, G12C).
- Metabolic Stability: Demonstrates an ex-vivo half-life in serum exceeding 40 hours.
- In Vitro Activity: High efficacy against several pancreatic cancer cell lines, including those with specific KRAS mutations.
- In Vivo Efficacy: Proven effectiveness in CDX animal models of pancreatic ductal adenocarcinoma.
Technology readiness level
This technology is at TRL 4, indicating that it has been validated in relevant laboratory settings, including preclinical models. Future work involves evaluating its efficacy and safety across diverse PDAC PDX models to identify responsive molecular subtypes, thereby advancing towards clinical application.
About University of Southern California
USC is a large, comprehensive private research university in Los Angeles, anchored by two urban campuses and an academic health system. Industry engages through applied research institutes such as the Information Sciences Institute, co-located engineering and clinical facilities, and flexible sponsored research contracting. Proximity to the region’s aerospace, media, and biotech corridors provides access to testbeds, talent, and pilot-scale partners across the greater L.A. innovation economy. Research is supported by competitive federal funding from NIH, NSF, and other major agencies alongside significant industry-sponsored awards. A dedicated technology transfer office supports IP strategy, licensing, corporate partnerships, and venture formation.
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