KRAS Mutant Protein-Protein Interaction Targets and Inhibitors for Cancer Therapy

Application

Immunotherapeutic agent and biosensor for KRAS^G12V mutation in tumor cells.

Key Benefits

• First in class, targeted immunotherapy for patients presented with KRAS^G12V mutation.
• Attenuates immune suppression associated with KRAS^G12V-positive cancers.

Market Summary

The KRAS^G12V mutation, representing 85% of all cancer mutations, is implicated in a wide variety of cancers including lung, pancreatic, thyroid, and colorectal cancers and is presented in 3% of all cancer patients. However, no drugs are available for treating patients with KRAS mutations. This suggests an urgent unmet clinical need for cancer therapeutics specifically targeting oncogenic KRAS mutations.

Technical Summary

Emory inventors have discovered that KRAS^G12V drives tumorigenesis in part through suppressing the JAK1-mediated immune response pathway. The inventors have constructed a small 8-mer peptide (“RasKi”) and showed that disruption of KRAS^G12V-JAK1 interaction enhances killing of KRAS^G12V-carrying cancer cells by restoring IFNγ-JAK1 mediated immune response. Thus, the KRAS^G12V-JAK1 interaction may represent a promising molecular target for therapeutic discovery and development. RasKi and its derivatives may serve as candidates for the development of the next generation of KRAS^G12V-targeted anticancer immune therapeutic agents for cancers with KRAS^G12V mutation.

Developmental Stage

In vitro study showing interaction between KRAS^G12V and JAK1.