Traditional cancer therapeutic combinations focus on targeting different signaling pathways and/or cellular processes at once. However, single agent-based targeting of a signaling pathway might not be sufficient for its inhibition. We have shown this for the PI3K/AKT pathway, where lymphoma cells normalized AKT activity within 24 hours even in the presence of a specific pathway inhibitors. To overcome this issue, we have developed a new approach that we called “vertical” signaling inhibition and showed that targeting PI3K/AKT pathway at multiple levels (multiple members) at the same time is synergistic, effective, and tolerated in vivo. Our results were just published in D1 journal!
Kupcova K, Senavova J, Jura F, Herman V, Rajmonova A, Pacheco-Blanco M,Chrbolkova T, Hamova I, Davis RE, Havranek O. Vertical targeting of the PI3K/AKT pathway at multiple points is synergistic and effective for non-Hodgkin lymphoma. Exp Hematol Oncol. 2024 Nov 1;13(1):108. doi: 10.1186/s40164-024-00568-6. (IF 9.4, Q1) [PubMed]
