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.
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.
Combination therapy of TRAIL and beclin 1 inhibitors presents a new therapeutic approach.