ArticleInvestigational new drugs2011
Hypoxia-targeting by tirapazamine (TPZ) induces preferential growth inhibition of nasopharyngeal carcinoma cells with Chk1/2 activation.
Article in Investigational new drugs, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- Dual-loaded niosome-dendrimer nanoplatform enhances Tirapazamine delivery to hypoxic breast cancer cells.Scientific reports · 2025Article
- Article
- Medicinal Chemistry of Drugs withJournal of medicinal chemistry · 2024Review
- Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Pretreatment Photopenia on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Scans Predicts Poor Prognosis in Nasopharyngeal Cancer Patients Undergoing Concurrent Chemoradiotherapy.Clinical and experimental otorhinolaryngology · 2020Article
- Three-dimensional perfused tumour spheroid model for anti-cancer drug screening.Biotechnology letters · 2016Article
- Genotoxic risk of quinocetone and its possible mechanism inToxicology research · 2016Article
- A Review: Proteomics in Nasopharyngeal Carcinoma.International journal of molecular sciences · 2015Review
- Synthesis, preferentially hypoxic apoptosis and anti-angiogenic activity of 1,2,4-benzotrazin-3-amine 1,4-dioxide bearing alkyl linkers with 1,2,4-benzotrazin-3-amine 1-oxide derivatives.Anti-cancer agents in medicinal chemistry · 2014Article
- From tumor hypoxia to cancer progression: the implications of hypoxia-inducible factor-1 expression in cancers.Anatomy & cell biology · 2012Article
- K252a induces anoikis-sensitization with suppression of cellular migration in Epstein-Barr virus (EBV)--associated nasopharyngeal carcinoma cells.Investigational new drugs · 2012Article
- Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca²⁺ balance protein levels.Oxidative medicine and cellular longevity · 2012Article
- Article
- Highly Active Nano-Reactor for Responding Tumor Microenvironment and Antitumor Therapy.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is commonly developed in solid tumors, which contributes to metastasis as well as radio- and chemo-resistance. Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic head and neck cancer prevalent in Southeast Asia with a high incidence rate of 15-30/100,000 persons/year (comparable to that of pancreatic cancer in the US). Previous clinical studies in NPC showed that hypoxia is detected in almost 100% of primary tumors and overexpression of hypoxia markers correlated with poor clinical outcome. Tirapazamine (TPZ) is a synthetic hypoxia-activated prodrug, which preferentially forms cytotoxic and DNA-damaging free radicals under hypoxia, thus selectively eradicate hypoxic cells. Here, we hypothesized that specific hypoxia-targeting by this clinical trial agent may be therapeutic for NPC. Our findings demonstrated that under hypoxia, TPZ was able to induce preferential growth inhibition of NPC cells, which was associated with marked cell cycle arrest at S-phase and PARP cleavage (a hallmark of apoptosis). Examination of S-phase checkpoint regulators revealed that Chk1 and Chk2 were selectively activated by TPZ in NPC cells under hypoxia. Hypoxia-selectivity of TPZ was also demonstrated by preferential downregulation of several important hypoxia-induced markers (HIF-1α, CA IX and VEGF) under hypoxia. Furthermore, we demonstrated that TPZ was equally effective and hypoxia-selective even in the presence of the EBV oncoprotein, LMP1 or the EBV genome. In summary, encouraging results from this proof-of-concept study implicate the therapeutic potential of hypoxia-targeting approaches for the treatment of NPC.
Indexed as
Identifiers
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.