Novel Therapeutics for Glioblastoma and Breast Cancer

Description:

Project ID:  D2011-38

 

Novelty:

Use of drug like molecules to induce cell death in drug resistant brain tumor and breast cancer cells via methuosis.

 

Value Propostion:

Despite recent advances in developing therapeutic agents that target cancer cells, scientists are facing challenges to cure cancer completely. The efforts are limited because of the mutations harbored by cancer cells that make them insensitive to apoptosis and also because of the development of multi-drug resistance in cancer cells.  Thus, there is a need to identify alternative cell death pathways that might be used to kill tumor cells that have ceased to respond to drugs that depend on induction of apoptotic mechanisms.

The disclosed invention is the composition of drug molecules that can effectively induce methuosis - an alternative and recently discovered cell death pathway, in the cancer cells. Methuosis (meaning intoxication to death) is a unique form of necrotic cell death characterized by massive accumulation of vacuoles derived from endosomes or micropinosomes. Via the mechanism of methuosis, these drug molecules have shown to kill temozolomide-resistant glioblastoma cells and doxorubicin-resistant breast cancer cells. The other advantages of this invention are:

·       Cells treated with molecule lose viability within 2-3 days.

·       Displacement of much of the cytoplasmic space by the vacuoles is accompanied by a decline in metabolic activity and a necrosis-like rupture of the cell.

·       Identified molecules can serve as prototypes for new drugs that can be used to induce non-apoptotic death in cancers that have become refractory to agents that work through DNA damage and apoptotic mechanisms.

·       May be useful in treating cancers of the brain, lung, liver, spleen, kidney, lymph node, small intestine, pancreas, blood cell, bone, colon, stomach, breast, endometrium, prostate, testicle, ovary, central nervous system, skin, head and neck, esophagus, or bone marrow.

 

Invention Description:

The Maltese laboratory at The University of Toledo discovered for the first time, the new pathway for cell death that is distinct from the classical cell death mechanism known as apoptosis. This pathway, coined as methuosis, is initiated by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of cell. The researchers further discovered new drug like molecules that can induce methuosis even in drug resistant glioblastoma and breast cancer cells. Specifically, they have shown the effect of these drug molecules on temozolomide-resistant U251 glioblastoma and doxorubicin-resistant MCF-7 breast carcinoma cells. Dr. Maltese laboratory has recently received a $1.4 million NIH grants to advance this research.

 

Looking for Partners: To develop and commercialize this technology as lead cancer therapeutics.

 

Patents: U.S. Utility Patent #9,028,796; U.S. Utility Patent #9,023,871, U.S. Utility Patent #9,061,994

Publications:

A Chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells.

Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell death.

Video:  UT Researcher Discovers New Weapon to Treat Brain Cancer

Patent Information:
For Information, Contact:
Stephen Snider
AVP Tech Transfer
The University of Toledo
419 530 6225
Stephen.Snider@utoledo.edu
Inventors:
William Maltese
Paul Erhardt
Jean Overmeyer
Michael Robinson
Keywords:
Brain tumor
Breast Cancer
Cancer
Glioblastoma
Methuosis