Preclinical Activity of a Novel Triple-Axis Inhibitor in B-cell Malignancies

Author

Rolando Martinez-Rico Jr, University of Nebraska Medical CenterFollow
Audrey Smith, University of Nebraska Medical CenterFollow
Dalia El-Gamal, University of Nebraska Medical CenterFollow

Files

Presentation date

Summer 8-11-2023

College, Institute, or Department

Eppley Institute for Research in Cancer

Faculty Mentor

Dalia El-Gamal

Research Mentor

Audrey Smith

Abstract

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are characterized by CD5+ B-cell accumulation in secondary lymphoid tissues. MCL and CLL B-cells depend upon B-cell receptor (BCR) signaling, tumor microenvironment support, and defective apoptosis mechanisms for expansion and survival. Targeted inhibitors of key proteins involved in proliferation/survival signaling (BTK, PI3K, BCL2) are commonly used in patients. However, multi-therapy resistant MCL and CLL underscores the need for novel therapeutic approaches. Recent studies have demonstrated pre-clinical activity of triple-axis inhibitors capable of concomitantly disrupting PI3K and BTK kinase activity and BRD4-mediated oncogene expression in B-cell malignancies. Here, we demonstrate the enhanced efficacy of a next-generation triple inhibitor (TRPi) in incurable, aggressive (MCL) and indolent (CLL) B-cell malignancies.

Keywords

mantle cell lymphoma; chronic lymphocytic leukemia; targeted multi-axis treatment; novel BTK/PI3K/BRD4 inhibitor

Recommended Citation

Martinez-Rico, Rolando Jr; Smith, Audrey; and El-Gamal, Dalia, "Preclinical Activity of a Novel Triple-Axis Inhibitor in B-cell Malignancies" (2023). Posters: 2023 Summer Undergraduate Research Program. 5.
https://digitalcommons.unmc.edu/surp2023/5