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Targeted cell membrane association for enhancing cancer cell therapies

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This technology selectively targets NRAS mutants in melanomas through depalmitoylation modulation, which can be used to treat cutaneous melanomas and other pathophysiological conditions.

Unmet Need: Effective therapeutic strategies for targeting NRAS mutants in melanoma

NRAS mutations are implicated in 15-20% of melanomas. Despite the significance of this mutation, targeting NRAS proteins has proven challenging due to undruggable sites on the protein surface. Thus, current treatments for NRAS-mutant melanomas focus on broad targeting of signaling pathways, which can have limited specificity and efficacy. Existing therapies also struggle to effectively modulate the palmitoylation cycle that governs NRAS membrane association. A more targeted and precise method to disrupt NRAS signaling could improve treatment efficacy and patient outcomes.

The Technology: Selective targeting of NRAS mutants by depalmitoylation modulation

This technology selectively targets NRAS-mutant proteins by modulating their palmitoylation cycle, disrupting NRAS membrane association and downstream signaling. By incorporating a feedback loop based on ERK phosphorylation, the technology selectively affects NRAS mutants without interfering with normal cellular processes. This approach ensures that NRAS signaling is disrupted in cancerous cells while minimizing effects on healthy tissue.

This technology has been validated in rat hippocampal neurons.

Applications:

  • Therapeutic development for cutaneous melanomas with RAS mutations
  • Drug discovery for NRAS-related cancers
  • Research model for cutaneous melanomas with RAS mutations
  • Research model for precision medicine in cancer treatment
  • Therapeutic for neurodegenerative diseases, cardiovascular diseases, and viral infections

Advantages:

  • Disrupts NRAS membrane association
  • Utilizes a sophisticated feedback loop based on ERK phosphorylation
  • Selectively targets NRAS mutants
  • Introduces a distinctive depalmitoylation modulation approach
  • High specificity
  • Can be either inducible or constitutive
  • Reduces side-effects
  • Broadly applicable

Lead Inventor:

Manu Ben Johny, Ph.D.

Patent Information:

Patent Pending

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