Trial reportClinical and translational science2021
SMAD4 loss is associated with response to neoadjuvant chemotherapy plus hydroxychloroquine in patients with pancreatic adenocarcinoma.
Trial report in Clinical and translational science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 18 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.
Phase I/II Study of Preoperative Gemcitabine in Combination With Oral Hydroxychloroquine (GcHc) in Subjects With High Risk Stage IIb or III Adenocarcinoma of the Pancreas
Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine
Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine.Cell reports. Medicine · 2025Trial
- Unexpected Long-Term Survival in Resected Pancreatic Ductal Adenocarcinoma Harboring KRAS G12R with an Ultra-Low-VAF SMAD4 Mutation: A Case Report and Mini-Review.Reports (MDPI) · 2026Article
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.Journal of molecular cell biology · 2026Article
- MOREshiny: a user-friendly application for the inference of phenotype-specific multi-omic regulatory networks.Bioinformatics advances · 2026Article
- Spatio-temporal processes in autophagosome-lysosome fusion.Medical review (2021) · 2025Review
- Review
- Review
- Echinacoside ameliorates hepatic fibrosis and tumor invasion in rats with thioacetamide-induced hepatocellular carcinoma.Biomolecules & biomedicine · 2024Article
- Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer.Current issues in molecular biology · 2024Review
- Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment.International journal of molecular sciences · 2024Review
- Pharmacology Progresses and Applications of Chloroquine in Cancer Therapy.International journal of nanomedicine · 2024Review
- Emerging horizons on molecular and circulating biomarkers in pancreatic adenocarcinoma.Frontiers in oncology · 2024Review
- Review
- Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression.The journal of pathology. Clinical research · 2023Article
- Recent advances in targeting autophagy in cancer.Trends in pharmacological sciences · 2023Review
- Multiple roles of mothers against decapentaplegic homolog 4 in tumorigenesis, stem cells, drug resistance, and cancer therapy.World journal of stem cells · 2022Review
- TGFβ Signaling in the Pancreatic Tumor Microenvironment.Cancers · 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
10 authors at 5 institutions in 1 country.
Funding
Abstract
SMAD4, a tumor suppressor gene, is lost in up to 60%-90% of pancreatic adenocarcinomas (PDAs). Loss of SMAD4 allows tumor progression by upregulating autophagy, a cell survival mechanism that counteracts apoptosis and allows intracellular recycling of macromolecules. Hydroxychloroquine (HCQ) is an autophagy inhibitor. We studied whether HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. We retrospectively analyzed the SMAD4 status of patients with PDA enrolled in two prospective clinical trials evaluating pre-operative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ (NCT01128296). More recently, a randomized trial of gemcitabine/nab-paclitaxel +/- HCQ evaluated Evans Grade histopathologic response (NCT01978184). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher's exact test and log-rank test were used to assess response and survival. Fifty-two patients receiving HCQ with neoadjuvant chemotherapy were studied. Twenty-five patients had SMAD4 loss (48%). 76% of HCQ-treated patients with SMAD4 loss obtained a histopathologic response greater than or equal to 2A, compared with only 37% with SMAD4 intact (p = 0.006). Although loss of SMAD4 has been associated with worse outcomes, in the current study, loss of SMAD4 was not associated with a detriment in median overall survival in HCQ-treated patients (34.43 months in SMAD4 loss vs. 27.27 months in SMAD4 intact, p = 0.18). The addition of HCQ to neoadjuvant chemotherapy in patients with PDA may improve treatment response in those with SMAD4 loss. Further study of the relationship among SMAD4, autophagy, and treatment outcomes in PDA is warranted.
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What OpenQuestion holds
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.