Enhancing the Therapeutic Potential of mTOR Inhibitors in Breast Cancer: Overcoming Therapy Resistance in TNBC

Principal Investigator: 

John Blenis, Anna-Maria and Stephen Kellen Professor in Cancer Research

Summary

  • Triple negative breast cancer (TNBC) is rare cancer that affects about 13 in 100,000 women each year
  • Dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway has been linked to cancer pathogenesis and is therefore an important target for cancer therapy
  • Dr. Blenis, has deep expertise in studying the mTOR pathway and its role in cancer progression
  • The Blenis lab aims to further elucidate how various nutrient inputs influence the signaling dynamics of mTOR and how this could be a powerful strategy for overcoming the processes that drives therapy resistance

Technical Overview

  • mTOR is a crucial signaling pathway that is essential in regulating cell survival, proliferation, and metabolism
  • mTOR acts in two functionally distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)
  • The Blenis lab believes that both pathways can sense dietary lipids in the form of ω-6 and ω-3 fatty acids
  • Both fatty acids are implicated in a range of disorders. ω-6 FAs are predominantly associated with the synthesis of pro-inflammatory prostaglandins, while ω-3 FAs have anti-inflammatory properties
  • The Blenis lab plans to characterize the effects of ω-6 and ω-3 FAs on mTOR signaling
  • They will then identify the metabolic mechanisms linking essential FAs with mTOR activity and therapy resistance
  • Finally, they will evaluate the synergism between modulating essential FA metabolism and mTOR inhibitor treatment in TNBC

Market Opportunity

  • TNBC is notoriously difficult to treat because it does not respond to traditional hormonal therapy
  • The TNBC market is forecasted to value over 800 million by 2028 with a CAGR of 5.3%
  • The Blenis lab will identify new and actionable metabolic determinants of drug resistance in TNBC, and will be impactful in two main ways:
  1. It will mechanistically characterize essential FAs as a key and novel nutrient input to mTOR
  2. It will reveal an entirely new way of repurposing first and second-generation mTOR inhibitors in the context of specific dietary modifications that unlock their therapeutic potential as a cancer treatment

Partnering Opportunity

Weill Cornell Medicine is seeking an industrial partner with deep domain expertise in the oncology space to advance research into the role of nutritional factors on mTOR and their role in TNBC

Schematic of the role of ω-6 and ω-3 FAs on tumor development.

Figure 1: Schematic of the role of ω-6 and ω-3 FAs on tumor development.



Contact Information

Dr. Jeff James

For additional information please contact

Jeffrey James
Associate Director, Business Development and Licensing
Phone: (646) 962-4194
Email: jaj268@cornell.edu