ArticleCancer chemotherapy and pharmacology2008
In vitro and in vivo effects of the conformationally restricted polyamine analogue CGC-11047 on small cell and non-small cell lung cancer cells.
Article in Cancer chemotherapy and pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis.International journal of molecular sciences · 2024Review
- A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy.Asian journal of pharmaceutical sciences · 2024Article
- Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs.International journal of molecular sciences · 2024Review
- Polyamine-Based Nanostructures Share Polyamine Transport Mechanisms with Native Polyamines and Their Analogues: Significance for Polyamine-Targeted Therapy.Medical sciences (Basel, Switzerland) · 2022Article
- Polyamines in cancer: integrating organismal metabolism and antitumour immunity.Nature reviews. Cancer · 2022Review
- Expanded Potential of the Polyamine Analogue SBP-101 (Diethyl Dihydroxyhomospermine) as a Modulator of Polyamine Metabolism and Cancer Therapeutic.International journal of molecular sciences · 2022Article
- Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents.Molecules (Basel, Switzerland) · 2022Article
- The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies.International journal of molecular sciences · 2022Review
- Recent Advances in the Synthesis of Polyamine Derivatives and Their Applications.Molecules (Basel, Switzerland) · 2021Review
- A Phase Ib multicenter, dose-escalation study of the polyamine analogue PG-11047 in combination with gemcitabine, docetaxel, bevacizumab, erlotinib, cisplatin, 5-fluorouracil, or sunitinib in patients with advanced solid tumors or lymphoma.Cancer chemotherapy and pharmacology · 2021Article
- Polyamine metabolism and cancer: treatments, challenges and opportunities.Nature reviews. Cancer · 2018Review
- Oil for the cancer engine: The cross-talk between oncogenic signaling and polyamine metabolism.Science advances · 2018Review
- Biochemical evaluation of the anticancer potential of the polyamine-based nanocarrier Nano11047.PloS one · 2017Article
- Targeting polyamine metabolism for cancer therapy and prevention.The Biochemical journal · 2016Review
- Histone deacetylase inhibition overcomes drug resistance through a miRNA-dependent mechanism.Molecular cancer therapeutics · 2013Article
- Polyamines and cancer: implications for chemotherapy and chemoprevention.Expert reviews in molecular medicine · 2013Review
- Polyamine pathway inhibition as a novel therapeutic approach to treating neuroblastoma.Frontiers in oncology · 2012Article
- Article
- Initial testing (stage 1) of the polyamine analog PG11047 by the pediatric preclinical testing program.Pediatric blood & cancer · 2011Article
- Current status of the polyamine research field.Methods in molecular biology (Clifton, N.J.) · 2011Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposePolyamines are essential for normal growth; however, the requirement for, and the metabolism of, polyamines are frequently dysregulated in cancer. Polyamine analogues have demonstrated promising preclinical results in multiple model systems of cancer, but their clinical utility has been limited by apparent toxicity. A representative compound of a new generation of short chain, conformationally restricted polyamine analogues, CGC-11047 has been synthesized and ongoing phase I clinical trials indicate it to be well tolerated at weekly doses of 610 mg (dose escalation is still in progress). Therefore, studies were designed to gain a better understanding of its effects on cellular polyamine biochemistry and efficacy in the treatment of human lung cancer models in vitro and in vivo.
methodsHuman lung cancers cell lines representing non-small cell and small cell lung cancers were investigated for their growth and biochemical response to CGC-11047. Effects of in vitro treatment with CGC-11047 on cell growth, the activity of the polyamine biosynthetic enzyme ornithine decarboxylase (ODC), and the expression and activity of the polyamine catabolic enzymes spermidine/spermine N(1)-acetyltransferase (SSAT) and spermine oxides (SMO) were measured. Additionally, the overall effects on intracellular polyamine pools were monitored. Finally, the in vivo efficacy of CGC-11047 in the treatment of a nude mouse model of human non-small cell lung cancer was evaluated.
resultsCGC-11047 effectively inhibited the growth of both small cell and non-small cell lung cancer cells in vitro. The greatest biochemical effects were observed in the non-small cell lung cancer cells where in addition to a profound down regulation of ODC activity, there was a significant increase in polyamine catabolism leading to a greater degree of polyamine pool depletion and greater accumulation of CGC-11047 when compared with the changes observed for the small cell lines. Importantly, CGC-11047 was found to be highly significant (P < 0.0001) in delaying the progression of established tumors in an in vivo model of human non-small cell lung cancer.
conclusionCGC-11047 represents a promising new polyamine analogue that warrants further preclinical and, potentially, clinical evaluation in lung cancer.
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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.