Targeting the ribosome to treat multiple myeloma.

CX-5461 MT: Regular Issue RNA polymerase I multiple myeloma panobinostat ribosome biogenesis

Journal

Molecular therapy. Oncology
ISSN: 2950-3299
Titre abrégé: Mol Ther Oncol
Pays: United States
ID NLM: 9918752083706676

Informations de publication

Date de publication:
21 Mar 2024
Historique:
received: 30 11 2023
revised: 31 01 2024
accepted: 02 02 2024
medline: 10 4 2024
pubmed: 10 4 2024
entrez: 10 4 2024
Statut: epublish

Résumé

The high rates of protein synthesis and processing render multiple myeloma (MM) cells vulnerable to perturbations in protein homeostasis. The induction of proteotoxic stress by targeting protein degradation with proteasome inhibitors (PIs) has revolutionized the treatment of MM. However, resistance to PIs is inevitable and represents an ongoing clinical challenge. Our first-in-human study of the selective inhibitor of RNA polymerase I transcription of ribosomal RNA genes, CX-5461, has demonstrated a potential signal for anti-tumor activity in three of six heavily pre-treated MM patients. Here, we show that CX-5461 has potent anti-myeloma activity in PI-resistant MM preclinical models

Identifiants

DOI: 10.1016/j.omton.2024.200771 PMID: 38596309 PMC: PMC10905045
pubmed: 38596309
doi: 10.1016/j.omton.2024.200771
pii: S2950-3299(24)00013-4
pmc: PMC10905045
doi:

Types de publication

Journal Article

Langues

eng

Pagination

200771

Informations de copyright

© 2024 The Author(s).

Déclaration de conflit d'intérêts

R.D.H. is a Chief Scientific Advisor to Pimera, Inc.

Auteurs

Kylee H Maclachlan (KH)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Kezia Gitareja (K)

St Vincent's Institute of Medical Research, Melbourne, VIC, Australia.
Department of Medicine- St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.

Jian Kang (J)

St Vincent's Institute of Medical Research, Melbourne, VIC, Australia.
Department of Medicine- St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.

Andrew Cuddihy (A)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Yuxi Cao (Y)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Nadine Hein (N)

The ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.

Carleen Cullinane (C)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Ching-Seng Ang (CS)

The Bio21 Institute of Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC, Australia.

Natalie Brajanovski (N)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Richard B Pearson (RB)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.

Amit Khot (A)

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Elaine Sanij (E)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
St Vincent's Institute of Medical Research, Melbourne, VIC, Australia.
Department of Medicine- St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.

Ross D Hannan (RD)

The ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.

Gretchen Poortinga (G)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Simon J Harrison (SJ)

Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Classifications MeSH