Technology Bundle ID
TAB-3603

Use of beclin 1 Inhibitors, including 17-hydroxy Wortmannin, to Treat TRAIL-resistant Cancer

Applications
Linked ID
E-252-2017-0
Lead Inventors
Wei Zheng (NCATS)
Co-Inventors
Sheng Dai (NCATS)
ICs
This technology includes the use of a beclin 1 inhibitor, 17-hydroxy Wortmannin, for the treatment of TRAIL-resistant colon cancer. TRAIL (TNF-related apoptosis-inducing ligand) binds to death receptors (DR4/DR5) and activates apoptosis in cancer cells. Multiple clinical trials have focused on promoting TRAIL-induced death but have had a lack of efficacy due to TRAIL resistance developing quickly in cancer cells. Recent work has found that this resistance may be mediated by a lack of activation of the apoptosis/autophagy regulator beclin 1. A compound screen was performed to find inhibitors of beclin 1 and identified 17-hydroxy Wortmannin. We found that 17-hydroxy Wortmannin can completely overcome TRAIL's resistance due to increased beclin 1 level in resistant colon cancer cells.
Commercial Applications
Further clinical work investigating TRAIL therapy in combination with beclin 1 inhibitors, such as 17-hydroxy Wortmannin, may support the combination therapy as a new therapeutic approach to treat a subpopulation of TRAIL resistant cancer patients.
Competitive Advantages
Combination therapy of TRAIL and beclin 1 inhibitors presents a new therapeutic approach.

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