ArticleMolecular oncology2015
Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Chimeric Ad5/35 oncolytic adenovirus overcome preexisting neutralizing antibodies and enhance tumor targeting efficiency.Cancer gene therapy · 2025Article
- Article
- Optimizing cancer therapy: a review of the multifaceted effects of metronomic chemotherapy.Frontiers in cell and developmental biology · 2024Review
- A deep tabular data learning model predicting cisplatin sensitivity identifies BCL2L1 dependency in cancer.Computational and structural biotechnology journal · 2023Article
- Carvedilol targets β-arrestins to rewire innate immunity and improve oncolytic adenoviral therapy.Communications biology · 2022Article
- Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer.Cancer gene therapy · 2021Review
- Article
- NK Cells Augment Oncolytic Adenovirus Cytotoxicity in Ovarian Cancer.Molecular therapy oncolytics · 2020Article
- Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma.International journal of molecular sciences · 2019Article
- Histone deacetylase inhibitor trichostatin A sensitises cisplatin-resistant ovarian cancer cells to oncolytic adenovirus.Oncotarget · 2018Article
- Identification of long non-coding RNA signature for paclitaxel-resistant patients with advanced ovarian cancer.Oncotarget · 2017Article
- Article
- miR-30a-5p enhances paclitaxel sensitivity in non-small cell lung cancer through targeting BCL-2 expression.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Inhibition of CDK4 sensitizes multidrug resistant ovarian cancer cells to paclitaxel by increasing apoptosiss.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- Article
- ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells.British journal of cancer · 2016Article
- Evaluation of CD46 re-targeted adenoviral vectors for clinical ovarian cancer intraperitoneal therapy.Cancer gene therapy · 2016Article
- MiR-125a promotes paclitaxel sensitivity in cervical cancer through altering STAT3 expression.Oncogenesis · 2016Article
- Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Resistance to paclitaxel chemotherapy frequently develops in ovarian cancer. Oncolytic adenoviruses are a novel therapy for human malignancies that are being evaluated in early phase trials. However, there are no reliable predictive biomarkers for oncolytic adenovirus activity in ovarian cancer. We investigated the link between paclitaxel resistance and oncolytic adenovirus activity using established ovarian cancer cell line models, xenografts with de novo paclitaxel resistance and tumour samples from two separate trials. The activity of multiple Ad5 vectors, including dl922-947 (E1A CR2-deleted), dl1520 (E1B-55K deleted) and Ad5 WT, was significantly increased in paclitaxel resistant ovarian cancer in vitro and in vivo. This was associated with greater infectivity resulting from increased expression of the primary receptor for Ad5, CAR (coxsackie adenovirus receptor). This, in turn, resulted from increased CAR transcription secondary to histone modification in resistant cells. There was increased CAR expression in intraperitoneal tumours with de novo paclitaxel resistance and in tumours from patients with clinical resistance to paclitaxel. Increased CAR expression did not cause paclitaxel resistance, but did increase inflammatory cytokine expression. Finally, we identified dysregulated cell cycle control as a second mechanism of increased adenovirus efficacy in paclitaxel-resistant ovarian cancer. Ad11 and Ad35, both group B adenoviruses that utilise non-CAR receptors to infect cells, are also significantly more effective in paclitaxel-resistant ovarian cell models. Inhibition of CDK4/6 using PD-0332991 was able both to reverse paclitaxel resistance and reduce adenovirus efficacy. Thus, paclitaxel resistance increases oncolytic adenovirus efficacy via at least two separate mechanisms - if validated further, this information could have future clinical utility to aid patient selection for clinical trials.
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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.