ArticleLeukemia2020
Pan-RAF inhibition induces apoptosis in acute myeloid leukemia cells and synergizes with BCL2 inhibition.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia.bioRxiv : the preprint server for biology · 2025Article
- Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.Biomedicines · 2025Review
- Designing patient-oriented combination therapies for acute myeloid leukemia based on efficacy/toxicity integration and bipartite network modeling.Oncogenesis · 2024Article
- Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.Hematology reports · 2023Review
- Mechanisms of resistance to targeted therapies for relapsed or refractory acute myeloid leukemia.Experimental hematology · 2022Review
- Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.International journal of molecular sciences · 2022Review
- Refining AML Treatment: The Role of Genetics in Response and Resistance Evaluation to New Agents.Cancers · 2022Review
- Genomic landscape of hyperleukocytic acute myeloid leukemia.Blood cancer journal · 2022Article
- Bioluminescent Zebrafish Transplantation Model for Drug Discovery.Frontiers in pharmacology · 2022Article
- Recent Developments in Targeting RAS Downstream Effectors for RAS-Driven Cancer Therapy.Molecules (Basel, Switzerland) · 2021Review
- Pan-RAF inhibitor LY3009120 is highly synergistic with low-dose cytarabine, but not azacitidine, in acute myeloid leukemia withOncology letters · 2021Article
- Article
- Arsenic trioxide synergistically promotes the antileukaemic activity of venetoclax by downregulating Mcl-1 in acute myeloid leukaemia cells.Experimental hematology & oncology · 2021Article
- Pan-RAF Inhibition Shows Anti-Leukemic Activity inCancers · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pan-RAF inhibitors have shown promise as antitumor agents in RAS and RAF mutated solid cancers. However, the efficacy of pan-RAF inhibitors in acute myeloid leukemia (AML) has not previously been explored. In AML, the RAS-RAF-MEK-ERK (MAPK) pathway is one of the most aberrantly activated oncogenic pathways, but previous targeting of this pathway by MEK inhibitors has not proven effective in clinical trials. Here we show that pan-RAF inhibition, but not MEK inhibition, induced cell death in 29% of AML samples while being nontoxic toward healthy bone marrow cells. Mechanistically, pan-RAF inhibition downregulated MCL1 protein synthesis and induced apoptosis in cells dependent on MCL1 for their survival. Furthermore, the combination of a pan-RAF and a BCL2 inhibitor overcame resistance to either compound alone in AML cell lines, as well as synergized and induced long-term responses ex vivo in AML patient samples relapsed or refractory to azacitidine + venetoclax treatment. Together, our results indicate that pan-RAF inhibition, alone or in combination with BCL2 inhibition, is a promising treatment strategy for AML.
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