Sicklick Lab
Principal Investigator: Jason Keith Sicklick
Institution: University of California San Diego (La Jolla, CA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
PROJECT SUMMARY/ABSTRACT Gastrointestinal stromal tumors (GIST) are most often driven by oncogenic KIT mutations and are treated with FDA-approved tyrosine kinase inhibitors [TKIs, including imatinib (IM)] that target constitutively active KIT. However, these drugs are only modestly effective. Even in the treatment naïve setting, ≤10% of patients have complete responses to treatment. Thus, TKIs do not kill every tumor cell despite the absence of secondary resistance mutations in KIT. Data from our lab demonstrates that treatment naïve KIT mutant GIST contain subpopulations of IM-resistant “persister” tumor cells that lack KIT, but do express Kvβ1.1, the protein product of the KCNAB1 gene. Kvβ1.1 regulates the channel activity of pore-forming α-subunits in voltage-gated potassium channels (VGKCs) that allow cells to modulate plasma membrane potential and cell volume homeostasis that, in turn, critically affects processes central to cancer biology (cell cycle regulation, cell migration and invasion). FDA-approved in 2010 for treatment of multiple sclerosis, 4-AP (fampridine) blocks VGKCs to improve motor skills. We now find that 4-AP synergizes with IM in vitro and in a murine model…
Active NIH Awards
- 5R01CA292590-02: Prognostic and Therapeutic Roles of Voltage Gated Potassium Channels in Managing KIT Mutant Gastrointestinal Stromal Tumors (GIST) (2026)
- 5U01CA278470-03: National Succinate Dehydrogenase-deficient GIST Translational Research and Clinical Trial Consortium (2026)
- 1R01CA292590-01A1: Prognostic and Therapeutic Roles of Voltage Gated Potassium Channels in Managing KIT Mutant Gastrointestinal Stromal Tumors (GIST) (2025)
- 5U01CA278470-02: National Succinate Dehydrogenase-deficient GIST Translational Research and Clinical Trial Consortium (2025)
- 1U01CA278470-01A1: National Succinate Dehydrogenase-deficient GIST Translational Research and Clinical Trial Consortium (2024)
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