ArticleOncotarget2014
Oncobiguanides: Paracelsus' law and nonconventional routes for administering diabetobiguanides for cancer treatment.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- The Role of Mitochondrial Dysfunction in Hepatocellular Carcinoma: From Pathogenesis and Drug Resistance to Targeted Therapeutic Strategies.Journal of hepatocellular carcinoma · 2026Review
- Exploring the Mechanism of Adjuvant Treatment of Glioblastoma Using Temozolomide and Metformin.International journal of molecular sciences · 2022Article
- RETRACTED: Metformin and Breast Cancer: Where Are We Now?International journal of molecular sciences · 2022Review
- 1-n-heptyl-5-(3, 4-difluorophenyl) biguanide inhibits non-small cell lung cancer cell growth by downregulating the EGFR signaling pathways.American journal of translational research · 2021Article
- Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Review
- Article
- Novel application of metformin combined with targeted drugs on anticancer treatment.Cancer science · 2019Review
- Dual Inhibition of Pirarubicin-InducedFrontiers in pharmacology · 2019Article
- The antitumor properties of metformin and phenformin reflect their ability to inhibit the actions of differentiated embryo chondrocyte 1.Cancer management and research · 2019Article
- Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis.International journal of endocrinology · 2019Article
- The 150 most important questions in cancer research and clinical oncology series: questions 94-101 : Edited by Cancer Communications.Cancer communications (London, England) · 2018Article
- Metformin causes cancer cell death through downregulation of p53-dependent differentiated embryo chondrocyte 1.Journal of biomedical science · 2018Article
- Article
- Article
- Phenformin alone or combined with gefitinib inhibits bladder cancer via AMPK and EGFR pathways.Cancer communications (London, England) · 2018Article
- New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways.Cancer science · 2018Article
- Review
- Impact of diabetes mellitus on risk of cardiovascular disease and all-cause mortality: Evidence on health outcomes and antidiabetic treatment in United States adults.World journal of diabetes · 2016Article
- Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A).Oncotarget · 2016Article
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 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
"The dose makes the poison", the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to "diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to "oncobiguanides" with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides.
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