Cancer Therapy via Simultaneous Non-apoptotic Cell Death Mechanisms

Project ID: D2018-15 

Background

Most of current cancer therapy employs drugs that act through apoptotic signaling pathways. However, cancer cells often acquire mutations that can diminish apoptosis and lead to chemo-resistance when coupled with increased capacity for drug efflux and DNA repair. This results in chemotherapeutic failure especially in recurrent and aggressive tumors. There is, therefore, a need for therapeutics that can target cancer cells via non-apoptotic cell death mechanisms.

Invention Description

Researchers from the University of Toledo have developed compounds and methods to induce cancer cell death through a non-apoptotic approach via combined methuosis and autophagy markers. Methuosis, a recently identified non-apoptotic cell death mechanism, results from the displacement of cytoplasm by large fluid-filled vacuoles that are derived from macropinosomes. Simultaneously targeting both autophagy and methuosis (‘methuophagy’) represents an attractive strategy for development of cancer therapeutics, especially for apoptotic-resistant cancers.   

Applications

• The compounds may be used as drug delivery systems for large molecules and other therapeutics due to its ability to generate exosomes
• The compounds may be used as chemo-adjuvants in combination with conventional therapeutics that suffer from drug resistance, toxicity, poor pharmacokinetic profile and efficacy
• The compounds may also be used as prodrug systems and pharmacological probes

Advantages

• There are currently no drugs in the market that can simultaneously produce autophagy and methuosis in cells
• A large chemical space with a unique mechanism of cell death
• The novel compounds developed here are pharmacokinetically stable
• Unlike other methuosis-inducing drugs, these compounds are soluble and possess more drug-like properties

IP Status:                           Patent Pending