PKCβ Inhibitor MS-553 Displays Preclinical Efficacy in Both Treatment-Naïve and BTK Inhibitor–Resistant Chronic Lymphocytic Leukemia
This study identified and characterized PKCβ as a therapeutic target in CLL, including CLL resistant to BTKis. Inhibition of PKCβ suppressed both BCR and Wnt/β-catenin signaling, delayed disease progression in vivo, overcame BTKi resistance mechanisms, and enhanced response to BCL-2 inhibition. See related commentary by Jebaraj and Stilgenbauer, p. 21.
Authors
- Nicole R. Grieselhuber (ORCID: https://orcid.org/0000-0003-3495-5932)
- Samon Benrashid (ORCID: https://orcid.org/0009-0009-0465-0231)
- Jennifer Ann Woyach (ORCID: https://orcid.org/0000-0002-3403-9144)
- Elizabeth M. Muhowski (ORCID: https://orcid.org/0000-0002-6903-0668)
- Nitin Jain (ORCID: https://orcid.org/0000-0003-0114-8384)
- John R. Sanchez (ORCID: https://orcid.org/0000-0002-5362-1025)
- Rosa Lapalombella (ORCID: https://orcid.org/0000-0001-6916-9400)
- Janani Ravikrishnan (ORCID: https://orcid.org/0000-0003-0933-3883)
- Kerry Anne Rogers (ORCID: https://orcid.org/0000-0001-5748-7874)
- Deepa Sampath (ORCID: https://orcid.org/0000-0002-4366-8436)
- Kai Zhang (ORCID: https://orcid.org/0009-0008-4212-282X)
- Lianbo Yu (ORCID: https://orcid.org/0000-0002-2025-2585)
- Seema Ali Bhat (ORCID: https://orcid.org/0000-0001-7844-0856)
- Elizabeth Perry (ORCID: https://orcid.org/0009-0009-8325-4287)
- Michael R. Niesman (ORCID: https://orcid.org/0000-0002-6700-8985)
- Daisy Diaz Rohena (ORCID: https://orcid.org/0000-0001-6286-4910)
- Alexander He (ORCID: https://orcid.org/0009-0003-0274-7546)
- Shrilekha Misra (ORCID: https://orcid.org/0000-0001-9656-932X)
- Adam S. Kittai (ORCID: https://orcid.org/0000-0002-4891-6144)
- John C. Byrd (ORCID: https://orcid.org/0000-0002-8778-1000)
- Shanmugapriya Thangavadivel (ORCID: https://orcid.org/0000-0001-9542-9050)
- Arnau Peris (ORCID: https://orcid.org/0009-0002-9091-5679)
- James S. Blachly (ORCID: https://orcid.org/0000-0002-4275-5562)
- Sachet A. Shukla (ORCID: https://orcid.org/0000-0003-2445-3584)
- Britten Gordon (ORCID: https://orcid.org/0009-0006-8751-4435)
- Brandi R. Walker (ORCID: https://orcid.org/0009-0002-7068-8894)
- William G. Wierda (ORCID: https://orcid.org/0000-0002-7357-270X)
- Alexander Marr (ORCID: https://orcid.org/0000-0002-1448-7353)
- Jyotsna Singh (ORCID: https://orcid.org/0000-0002-1185-9588)
- Jazmin Urrutia (ORCID: https://orcid.org/0000-0002-0434-4308)
- Andrew D. Mitchell (ORCID: https://orcid.org/0000-0002-2018-4359)
- Tzung-Huei Lai (ORCID: https://orcid.org/0009-0002-4318-8042)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- The University of Texas at San Antonio Health Science Center (US)
- The Ohio State University Wexner Medical Center (US)
- SignalRx Pharmaceuticals (United States) (US)
- Ligand Pharmaceuticals (United States) (US)
- The Ohio State University (US)
- University of Cincinnati (US)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0114
- Citations
- 1
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 1.63