Targeting SREBP1 for Managing Acquired Resistance to Osimertinib/AZD9291 and Other EGFR Inhibitors for Non-small Cell Lung Cancer Treatment

­ Application Small molecule combination therapy (adjuvant, sensitizing agent) for Osimertinib (to treat non-small cell lung cancer with common EGFR activating mutations and T790M resistant mutation). Key Benefits Therapy against EGFR-TKI res…

Application
Small molecule combination therapy (adjuvant, sensitizing agent) for Osimertinib (to treat non-small cell lung cancer with common EGFR activating mutations and T790M resistant mutation).

Key Benefits

  • Therapy against EGFR-TKI resistant tumors with mutant EGFR (e.g., T790M).


Market Summary
Non-small cell lung cancer (NSCLC) accounts for 84% of all lung cancer cases in the U.S. Current treatments have no effects on most patients (American Cancer Society). NSCLC patients acquire resistance during treatment, caused by a new mutation (T790M) that alters drug binding and enzymatic activity of the mutant epidermal growth factor receptor (EGFR). Even patients treated with FDA-approved Osimertinib still inevitably develop acquired resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. Researchers at Emory University have developed a treatment against EGFR-TKI resistant tumors with EGFR mutations including T790M mutation through chemical inhibition of SREBP1 by using SREBP1 inhibitors when combined with AZD9291, synergistically decreasing the survival of AZD9291 resistant cells. This invention would contribute most to the non-small cell lung cancer market, which is estimated to reach $23.5 billion by 2023 at a CAGR of 7.9% from 2018-to 2023 (BCC Research PHM206A).

Technical Summary
This technology concerns the sensitization of AZD9291 resistant EGFR mutant NSCLC by inhibiting SERBP1. Researchers at Emory University have demonstrated that chemical inhibition of SREBP1 by using SREBP1 inhibitors when combined with AZD9291, decreased the survival of AZD9291 resistant cells. Researchers also discovered a previously unknown connection between SREBP1 and AZD9291 cancer therapy. Experiments have demonstrated that AZD9291 dramatically increases the levels of the mature form of SREBP1 (mSREBP1) and its targeted proteins through mSREBP1 degradation. Researchers concluded that AZD9291 effectively inhibits mTORC2 signaling and decreases mSREBP1 levels in EGFR mutant NSCLC cells.

Developmental Stage
Early-stage. Publication: 2021 National Lung Cancer SPORE Workshop (6/16/2021)

Website

https://emoryott.technologypublisher.com/techcase/20195

Contact Information

TTO Home Page: https://emoryott.technologypublisher.com

Name: Hyeon (Sean) Kim

Title: Licensing Associate

Email: hkim70@emory.edu

Phone: 404-727-7218