A new Ph.D. student
10/2024
We are happy that a new Ph.D., Mgr. Karin Ravaszova, just joined our group. She will be working on specifics of BCR signaling in lymphoma and with Dr. Huskova on her project focused on AID activity in solid cancers and associate histone mutations.
NOVEL CONCEPT - Vertical targeting of the PI3K/AKT pathway
9/2024
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. (2023 IF 9.4, D1) Full-text link
Impact of PIK3CA gain and PTEN loss in mantle cell lymphoma
8/2024
Within a collaborative project with prof. Klener, this study from Havranek laboratory described some of the key consequences associated with phosphatidylinositol 3-kinase / protein kinase B (PI3K/AKT) signaling pathway oncogenic activation. PI3K/AKT pathway is one of central cellular pathways which is frequently altered by PIK3CA amplifications and PTEN deletions in lymphomas. We have shown that in mantel cell lymphoma, its oncogenic activation associates with lower dependence on upstream activation, better metabolic and hypoxic adaptation, and targeted therapy resistance. All features of more aggressive tumor behavior with possible critical therapeutic consequences.
Bettazova N, Senavova J, Kupcova K, Sovilj D, Rajmonova A, Andera L, Svobodova K, Berkova A, Zemanova Z, Daumova L, Herman V, Dolnikova A, Davis RE, Trneny M, Klener P, Havranek O. Impact of PIK3CA gain and PTEN loss on mantle cell lymphoma biology and sensitivity to targeted therapies. Blood Adv. 2024 Oct 22;8(20):5279-5289 (2023 IF 7.4, Q1) Full-text link
