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Targeted Inhibition of Leukemia Inhibitory Factory (LIF)/LIFR Axis for the Treatment of Triple-Negative Breast Cancer

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Technical Report,01 Feb 2018,31 Jan 2019

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University of Texas Health Science Center at San Antonio San Antonio United States

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Leukemia inhibitory factor receptor LIFR and its ligand LIF play a critical role in cancer progression. Here, we describe a rationally designed first-in-class inhibitor of LIFR, EC359 that directly interacts with LIFR and effectively block LIFLIFR interactions. The results from first year studies showed that EC359 treatment exhibit anti-proliferative effects, reduce invasiveness and promote apoptosis of TNBC cells. The activity of EC359 is dependent on LIFR expression and treatment with EC359 attenuated the activation of LIFLIFR driven pathways including STAT3, mTOR, and AKT. EC359 significantly reduced tumor progression in TNBC xenografts. EC359 exhibited good ADME characteristics. Collectively, these data support EC359 as a novel targeted therapeutic that inhibits LIFR oncogenic signaling that occur in TNBC.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

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