ArticleFrontiers in oncology2022
Combining the SMAC mimetic LCL161 with Gemcitabine plus Cisplatin therapy inhibits and prevents the emergence of multidrug resistance in cholangiocarcinoma.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Apoptosis regulators of the Bcl-2 family play a key role in chemoresistance of cholangiocarcinoma organoids.International journal of cancer · 2025Article
- Necroptosis-driven T cell activation promotes IL-6-mediated PD-L1 upregulation in cholangiocarcinoma cells: IL-6 gene signature as a biomarker for chemo-immunotherapy response.Biology direct · 2025Article
- CDK4/6 inhibitors upregulate cIAP1/2, and Smac mimetic LCL161 enhances their antitumor effects in cholangiocarcinoma cells.Scientific reports · 2025Article
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- Smac/DIABLO protein acts as an independent prognostic factor in oral squamous cell carcinoma.Scientific reports · 2024Article
- Babaodan overcomes cisplatin resistance in cholangiocarcinoma via inhibiting YAP1.Pharmaceutical biology · 2024Article
- Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma.Cancer cell international · 2024Review
- A live single-cell reporter system reveals drug-induced plasticity of a cancer stem cell-like population in cholangiocarcinoma.Scientific reports · 2024Article
- Cisplatin in Liver Cancer Therapy.International journal of molecular sciences · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholangiocarcinoma (CCA) is a highly lethal gastrointestinal malignancy that has one of the worst prognoses among solid tumors. The combination of Gemcitabine + Cisplatin (GEM/CIS) remains the standard first-line treatment for advanced stage CCA. However, this drug combination yields only a modest objective response rate, and in cases that initially respond to this treatment, drug resistance commonly rapidly develops. To improve the efficiency of GEM/CIS therapy for CCA, a thorough understanding of the mechanism of GEM/CIS resistance in CCA is required. To that end - in this study, we developed several acquired GEM/CIS-resistant CCA cell lines and we screened those cell lines for acquired vulnerability. The screening process revealed that subset of CCA with GEM/CIS resistance acquired vulnerability to the small-molecule second mitochondrial-derived activator of caspases (SMAC) mimetics LCL161 and Birinapant. The observed acquired vulnerability was found to be associated with upregulation of an inhibitor of apoptosis protein 2 (cIAP2), a known target of SMAC mimetics. LCL161 or cIAP2-shRNA downregulated cIAP2 and restored the sensitivity to GEM/CIS in GEM/CIS-resistant CCA cell lines and in
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