ArticleOncotarget2015
Multistep, effective drug distribution within solid tumors.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed, 30 citations in OpenAlex.
- A Phase II Trial of an Extended-Release siRNA Implant Targeting KRASG12D/V in Locally Advanced Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Applying Ultrasound to Mechanically and Noninvasively Sensitize Prostate Tumors to TRAIL-Mediated Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- JHU-2545 preferentially shields salivary glands and kidneys during PSMA-targeted imaging.European journal of nuclear medicine and molecular imaging · 2025Article
- Transformable self-delivered supramolecular nanomaterials combined with anti-PD-1 antibodies alleviate tumor immunosuppression to treat breast cancer with bone metastasis.Journal of nanobiotechnology · 2024Article
- RNA-based Therapeutics: Past, Present and Future Prospects, Challenges in Cancer Treatment.Current pharmaceutical biotechnology · 2024Review
- A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics.Advanced drug delivery reviews · 2023Review
- Development of Injectable and Biodegradable Needle-Type Starch Implant for Effective Intratumoral Drug Delivery and Distribution.International journal of nanomedicine · 2022Article
- Sunitinib-Loaded Chondroitin Sulfate Hydrogels as a Novel Drug-Delivery Mechanism for the Treatment of Pancreatic Neuroendocrine Tumors.Annals of surgical oncology · 2021Article
- Recent Advances in the Delivery Carriers and Chemical Conjugation Strategies for Nucleic Acid Drugs.Cancers · 2021Review
- Modelling of combination therapy using implantable anticancer drug delivery with thermal ablation in solid tumor.Scientific reports · 2020Article
- Therapeutic siRNA: state of the art.Signal transduction and targeted therapy · 2020Review
- Development and Clinical Trials of Nucleic Acid Medicines for Pancreatic Cancer Treatment.International journal of molecular sciences · 2019Review
- The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market.Pharmaceutical research · 2017Review
- Theranostic Role ofTheranostics · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The distribution of drugs within solid tumors presents a long-standing barrier for efficient cancer therapies. Tumors are highly resistant to diffusion, and the lack of blood and lymphatic flows suppresses convection. Prolonged, continuous intratumoral drug delivery from a miniature drug source offers an alternative to both systemic delivery and intratumoral injection. Presented here is a model of drug distribution from such a source, in a multistep process. At delivery onset the drug mainly affects the closest surroundings. Such 'priming' enables drug penetration to successive cell layers. Tumor 'void volume' (volume not occupied by cells) increases, facilitating lymphatic perfusion. The drug is then transported by hydraulic convection downstream along interstitial fluid pressure (IFP) gradients, away from the tumor core. After a week tumor cell death occurs throughout the entire tumor and IFP gradients are flattened. Then, the drug is transported mainly by 'mixing', powered by physiological bulk body movements. Steady state is achieved and the drug covers the entire tumor over several months. Supporting measurements are provided from the LODER system, releasing siRNA against mutated KRAS over months in pancreatic cancer in-vivo models. LODER was also successfully employed in a recent Phase 1/2 clinical trial with pancreatic cancer patients.
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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.