ArticleBMC cancer2021
Inhibition of ERAD synergizes with FTS to eradicate pancreatic cancer cells.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- ERAD inhibitor Eeyarestatin I (EerI) suppresses duck plague virus by restoring STING-mediated antiviral immunity.Poultry science · 2026Article
- Crosstalk between KRAS and miRNAs in pancreatic cancer: Opportunities for its diagnosis, prognosis and therapeutic intervention (Review).International journal of oncology · 2026Review
- Identification of HSPE1 as a new actionable cancer vulnerability leads to an innovative and effective combination therapy for pancreatic ductal adenocarcinoma.Molecular cancer · 2026Article
- The Unfolded Protein Response-Novel Mechanisms, Challenges, and Key Considerations for Therapeutic Intervention.Cancers · 2025Review
- Targeting EGFR-binding protein SLC7A11 enhancing antitumor immunity of T cells via inducing MHC-I antigen presentation in nasopharyngeal carcinoma.Cell death & disease · 2025Article
- Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases.Molecular neurobiology · 2024Review
- CRISPRingCancers · 2024Review
- LMP2 and TAP2 impair tumor growth and metastasis by inhibiting Wnt/β-catenin signaling pathway and EMT in cervical cancer.BMC cancer · 2023Article
- Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections.Microorganisms · 2023Review
- VCP/p97, a pleiotropic protein regulator of the DNA damage response and proteostasis, is a potential therapeutic target inGenes & cancer · 2023Article
- mTOR inhibition attenuates chemosensitivity through the induction of chemotherapy resistant persisters.Nature communications · 2022Article
- GRP94 Inhabits the Immortalized Porcine Hepatic Stellate Cells Apoptosis under Endoplasmic Reticulum Stress through Modulating the Expression of IGF-1 and Ubiquitin.International journal of molecular sciences · 2022Article
- N6-methyladenosine-mediated CELF2 regulates CD44 alternative splicing affecting tumorigenesis via ERAD pathway in pancreatic cancer.Cell & bioscience · 2022Article
- Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway.International journal of molecular sciences · 2021Review
- Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- Pre-clinical Models of Metastasis in Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC), one of the most lethal cancers, is driven by oncogenic KRAS mutations. Farnesyl thiosalicylic acid (FTS), also known as salirasib, is a RAS inhibitor that selectively dislodges active RAS proteins from cell membrane, inhibiting downstream signaling. FTS has demonstrated limited therapeutic efficacy in PDAC patients despite being well tolerated.
methodsTo improve the efficacy of FTS in PDAC, we performed a genome-wide CRISPR synthetic lethality screen to identify genetic targets that synergize with FTS treatment. Among the top candidates, multiple genes in the endoplasmic reticulum-associated protein degradation (ERAD) pathway were identified. The role of ERAD inhibition in enhancing the therapeutic efficacy of FTS was further investigated in pancreatic cancer cells using pharmaceutical and genetic approaches.
resultsIn murine and human PDAC cells, FTS induced unfolded protein response (UPR), which was further augmented upon treatment with a chemical inhibitor of ERAD, Eeyarestatin I (EerI). Combined treatment with FTS and EerI significantly upregulated the expression of UPR marker genes and induced apoptosis in pancreatic cancer cells. Furthermore, CRISPR-based genetic ablation of the key ERAD components, HRD1 and SEL1L, sensitized PDAC cells to FTS treatment.
conclusionOur study reveals a critical role for ERAD in therapeutic response of FTS and points to the modulation of UPR as a novel approach to improve the efficacy of FTS in PDAC treatment.
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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.