ArticleBlood2007
Farnesyl transferase inhibitor resistance probed by target mutagenesis.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Trial
- Repurposing of lonafarnib as a treatment for SARS-CoV-2 infection.JCI insight · 2025Article
- Virus-assisted directed evolution of biomolecules.Current opinion in chemical biology · 2023Review
- Directed evolution in mammalian cells.Nature methods · 2021Review
- Article
- Prenylation inhibition-induced cell death in melanoma: reduced sensitivity in BRAF mutant/PTEN wild-type melanoma cells.PloS one · 2015Article
- Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia.Biologics : targets & therapy · 2008Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mutation in the target oncoprotein is a common mechanism of resistance to tyrosine kinase inhibitors, as exemplified by the many BCR/ABL mutations that thwart imatinib activity in patients with chronic myelogenous leukemia. It remains unclear whether normal cellular protein targets of chemotherapeutics will evolve drug resistance via mutation to a similar extent. We conducted an in vitro screen for resistance to lonafarnib, a farnesyl protein transferase inhibitor that blocks prenylation of a number of proteins important in cell proliferation, and identified 9 mutations clustering around the lonafarnib binding site. In patients treated with a combination of imatinib and lonafarnib, we identified farnesyl protein transferase mutations in residues identified in our screen. Substitutions at Y361 were found in patients prior to treatment initiation, suggesting that these mutants might confer a proliferative advantage to leukemia cells, which we were able to confirm in cell culture. In vitro mutagenesis of normal cellular enzymes can be exploited to identify mutations that confer chemotherapy resistance to novel agents.
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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.