{"entity": "publication", "iuid": "2f01a68ed08e4cabac444bd06a7efc05", "timestamp": "2026-08-23T09:24:56.498Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2f01a68ed08e4cabac444bd06a7efc05.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2f01a68ed08e4cabac444bd06a7efc05"}}, "title": "The ROCK-1/2 inhibitor RKI-1447 blocks N-MYC, promotes cell death, and emerges as a synergistic partner for BET inhibitors in neuroblastoma.", "authors": [{"family": "Pepich", "given": "Adena", "initials": "A"}, {"family": "T\u00fcmmler", "given": "Conny", "initials": "C"}, {"family": "Abu Ajamieh", "given": "Sara", "initials": "S"}, {"family": "Treis", "given": "Diana", "initials": "D"}, {"family": "Boje", "given": "Ammelie Svea", "initials": "AS"}, {"family": "Vellema", "given": "Quinty", "initials": "Q"}, {"family": "Tsea", "given": "Ioanna", "initials": "I"}, {"family": "\u00c5kerlund", "given": "Emma", "initials": "E"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B"}, {"family": "Shirazi Fard", "given": "Shahrzad", "initials": "S"}, {"family": "Kogner", "given": "Per", "initials": "P"}, {"family": "Johnsen", "given": "John Inge", "initials": "JI"}, {"family": "Wickstr\u00f6m", "given": "Malin", "initials": "M"}], "type": "journal article", "published": "2024-11-28", "journal": {"title": "Cancer Lett.", "issn": "1872-7980", "volume": "605", "pages": "217261", "issn-l": "0304-3835"}, "abstract": "High-risk neuroblastoma has a poor prognosis despite intensive treatment, highlighting the need for new therapeutic strategies. Genetic alterations in activators and inactivators of Rho GTPase have been identified in neuroblastoma suggested to activate Rho/Rho-kinase (ROCK) signaling. ROCK has also been implicated in therapy resistance. Therefore, we have explored the efficacy of the dual ROCK inhibitor RKI-1447 in neuroblastoma, emphasizing combination strategies. Treatment with RKI-1447 resulted in decreased growth, increased cell death, and inhibition of N-MYC in vitro and in vivo. A combination screen revealed enhanced effects between RKI-1447 and BET inhibitors. Synergistic effects from RKI-1447 and the BET inhibitor, ABBV-075, were confirmed in various neuroblastoma models, including zebrafish. Interestingly, ABBV-075 increased phosphorylation of both myosin light chain 2 and cofilin, downstream effectors of ROCK, increases that were blocked by adding RKI-1447. The combination treatment also augmented an inhibitory effect on C-MYC and, less pronounced, N-MYC protein expression. BET inhibitors have shown preclinical efficacy against neuroblastoma, but acquired resistance has limited their therapeutic benefit. We reveal that the combination of ROCK and BET inhibitors offers a promising treatment approach that can potentially mitigate resistance to BET inhibitors and reduce toxicity.", "doi": "10.1016/j.canlet.2024.217261", "pmid": "39307412", "labels": [], "xrefs": [{"db": "pii", "key": "S0304-3835(24)00656-6"}], "notes": [], "created": "2026-08-20T06:49:39.117Z", "modified": "2026-08-20T06:49:39.153Z"}