Methods and compositions for the treatment of glutamine-addicted cancers
Patent Number: US20160022708
Executive Summary:
General Description:
Neuroblastoma and Ewing’s sarcoma, together cause 18% of all pediatric cancer death. This novel combination therapy exploits glutamine addiction – particularly associated with Myc deregulation – to specifically kill tumor cells.
Scientific Progress: In vitro and in mouse xenograft models, high-Myc expressing tumors are susceptible to DON-induced apoptosis. Antagonists to Bcl-2 family members synergize the cytotoxic effect of DON.
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Legal Status: Pending
Publication PMID: 25615615
Publications:
Olsen RR, Mary-Sinclair MN, Yin Z, Freeman KW. Antagonizing Bcl-2 family members sensitizes neuroblastoma and Ewing's sarcoma to an inhibitor of glutamine metabolism. PLoS One. 2015 Jan 23;10(1):e0116998. doi: 10.1371/journal.pone.0116998. eCollection 2015.
Inventor Bio: Kevin Freeman
https://www.stjude.org/directory/f/kevin-freeman.html
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: US Grant
- Patent Link: https://patents.google.com/patent/US20160022708/
- Research Institute: St. Jude Children’s Research Hospital
- Disease Focus: Glutamine-addicted cancers, including neuroblastoma or Ewing’s sarcoma
- Basis of Invention: Combining a glutaminase antagonist and a pro-apoptotic compound causes synergistic cytotoxicity
- How it works: The glutaminase antagonist is 6-diazo-5-oxo-1-norleucine (DON) and the pro-apoptotic compound is a Bcl-2 family member antagonist (obatoclax mesylate, navitoclax, or fenretinide)
- Lead Challenge Inventor: Kevin Freeman
- Development Stage: Preclinical (mouse xenograft models)
- Novelty: Novel combination therapy
- Clinical Applications: Treatment of neuroblastoma or Ewing’s sarcoma
General Description:
Neuroblastoma and Ewing’s sarcoma, together cause 18% of all pediatric cancer death. This novel combination therapy exploits glutamine addiction – particularly associated with Myc deregulation – to specifically kill tumor cells.
Scientific Progress: In vitro and in mouse xenograft models, high-Myc expressing tumors are susceptible to DON-induced apoptosis. Antagonists to Bcl-2 family members synergize the cytotoxic effect of DON.
Future Directions:
- Clinical trial
Strengths:
- Those drugs are FDA-approved or in clinical trials, therefore the PK/PD and the side effects are known in human
- New clinical indications
Weaknesses:
- Combination therapy of commercially available drugs
Patent Status:
Legal Status: Pending
- Priority date: 2013.03.14
- Filing date: 2014.03.13
- Publication date: 2016.01.28
Publication PMID: 25615615
Publications:
Olsen RR, Mary-Sinclair MN, Yin Z, Freeman KW. Antagonizing Bcl-2 family members sensitizes neuroblastoma and Ewing's sarcoma to an inhibitor of glutamine metabolism. PLoS One. 2015 Jan 23;10(1):e0116998. doi: 10.1371/journal.pone.0116998. eCollection 2015.
Inventor Bio: Kevin Freeman
https://www.stjude.org/directory/f/kevin-freeman.html
