ArticleJournal of the National Cancer Institute2012
Selective inhibition of HER2-positive breast cancer cells by the HIV protease inhibitor nelfinavir.
Article in Journal of the National Cancer Institute, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
- Trial
- Revolutionising Neurological Therapeutics: Investigating Drug Repurposing Strategies.CNS & neurological disorders drug targets · 2025Review
- HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.British journal of cancer · 2024Article
- Unraveling anticancer potential of a novel serine protease inhibitor from marine yeast Candida parapsilosis ABS1 against colorectal and breast cancer cells.World journal of microbiology & biotechnology · 2023Article
- Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC TransporterCells · 2023Article
- Drug-Repurposing Screening Identifies a Gallic Acid Binding Site on SARS-CoV-2 Non-structural Protein 7.ACS pharmacology & translational science · 2023Article
- Immune microenvironment dynamics of HER2 overexpressing breast cancer under dual anti-HER2 blockade.Frontiers in immunology · 2023Article
- Proteomic Analysis of HCC-1954 and MCF-7 Cell Lines Highlights Crosstalk between αv and β1 Integrins, E-Cadherin and HER-2.International journal of molecular sciences · 2022Article
- Article
- Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning.Acta pharmaceutica Sinica. B · 2022Article
- Glioblastoma and the search for non-hypothesis driven combination therapeutics in academia.Frontiers in oncology · 2022Review
- Molecular Mechanisms of HIV Protease Inhibitors Against HPV-Associated Cervical Cancer: Restoration ofFrontiers in molecular biosciences · 2022Review
- Article
- Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma.Cancer research · 2021Article
- The disruption of protein-protein interactions with co-chaperones and client substrates as a strategy towards Hsp90 inhibition.Acta pharmaceutica Sinica. B · 2021Review
- Review
- Bruceantin targets HSP90 to overcome resistance to hormone therapy in castration-resistant prostate cancer.Theranostics · 2021Article
- Review
- Efavirenz induces DNA damage response pathway in lung cancer.Oncotarget · 2020Article
- Modulation of mTORC1 Signaling Pathway by HIV-1.Cells · 2020Review
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7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is highly aggressive and has higher risk of recurrence than HER2-negative cancer. With few treatment options available, new drug targets specific for HER2-positive breast cancer are needed.
methodsWe conducted a pharmacological profiling of seven genotypically distinct breast cancer cell lines using a subset of inhibitors of breast cancer cells from a screen of the Johns Hopkins Drug Library. To identify molecular targets of nelfinavir, identified in the screen as a selective inhibitor of HER2-positive cells, we conducted a genome-wide screen of a haploinsufficiency yeast mutant collection. We evaluated antitumor activity of nelfinavir with xenografts in athymic nude mouse models (n = 4-6 per group) of human breast cancer and repeated mixed-effects regression analysis. All statistical tests were two-sided.
resultsPharmacological profiling showed that nelfinavir, an anti-HIV drug, selectively inhibited the growth of HER2-positive breast cancer cells in vitro. A genome-wide screening of haploinsufficiency yeast mutants revealed that nelfinavir inhibited heat shock protein 90 (HSP90) function. Further characterization using proteolytic footprinting experiments indicated that nelfinavir inhibited HSP90 in breast cancer cells through a novel mechanism. In vivo, nelfinavir selectively inhibited the growth of HER2-positive breast cancer cells (tumor volume index of HCC1954 cells on day 29, vehicle vs nelfinavir, mean = 14.42 vs 5.16, difference = 9.25, 95% confidence interval [CI] = 5.93 to 12.56, P < .001; tumor volume index of BT474 cells on day 26, vehicle vs nelfinavir, mean = 2.21 vs 0.90, difference = 1.31, 95% CI = 0.83 to 1.78, P < .001). Moreover, nelfinavir inhibited the growth of trastuzumab- and/or lapatinib-resistant, HER2-positive breast cancer cells in vitro at clinically achievable concentrations.
conclusionNelfinavir was found to be a new class of HSP90 inhibitor and can be brought to HER2-breast cancer treatment trials with the same dosage regimen as that used among HIV patients.
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