ArticleOncotarget2020
Paradox breaker BRAF inhibitors have comparable potency and MAPK pathway reactivation to encorafenib in BRAF mutant colorectal cancer.
Article in Oncotarget, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- A New Era of Salvage-Line Treatment for Metastatic Colorectal Cancer: The Role and Clinical Significance of Circulating Tumor DNA.Biomolecules · 2026Review
- Novel RAF-directed approaches to overcome current clinical limits and block the RAS/RAF node.Molecular oncology · 2024Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Review
- A Phase Ib/II Trial of Combined BRAF and EGFR Inhibition in BRAF V600E Positive Metastatic Colorectal Cancer and Other Cancers: The EVICT (Erlotinib and Vemurafenib In Combination Trial) Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The Genomic Environment ofJournal of clinical medicine · 2022Article
- Development of a potent small-molecule degrader against oncogenic BRAFCancer science · 2022Article
- Anti-tumor activity of the pan-RAF inhibitor TAK-580 in combination with KPT-330 (selinexor) in multiple myeloma.International journal of hematology · 2022Article
- Looking Beyond the Glioblastoma Mask: Is Genomics the Right Path?Frontiers in oncology · 2022Review
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The BEACON CRC trial demonstrated a survival advantage over chemotherapy for a combination of targeted agents comprising the potent BRAF inhibitor encorafenib together with cetuximab and binimetinib. Resistance to BRAF inhibition in CRC arises in part through the generation and activation of RAF dimers resulting in MEK-ERK pathway reactivation. Paradox breaker BRAF inhibitors, such as PLX8394, are designed to inhibit RAF dimer formation. We analyzed whether paradox breakers reduce pathway reactivation and so have enhanced potency compared with encorafenib in BRAF mutant CRC. The potency of encorafenib and PLX8394 was greater than vemurafenib and the degree of pathway reactivation somewhat less. However, dose response curves for encorafenib and PLX8394 were similar and there was no significant differences in degree of pathway reactivation. To our knowledge these data represent the first comparative data of encorafenib and paradox breaker inhibitors in BRAF mutant CRC. Whilst these results support further investigation of PLX8394, all three agents tested reactivated the pathway in melanoma cells, a disease in which monotherapy is effective. Strategies focused on restricting RAF dimerization fail to address the impact that specific context of BRAF mutation in CRC has on targeted therapy outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.