Oncobiguanides: Paracelsus' law and nonconventional routes for administering diabetobiguanides for cancer treatment
dc.contributor.author
dc.date.accessioned
2014-06-30T10:43:52Z
dc.date.available
2014-06-30T10:43:52Z
dc.date.issued
2014
dc.identifier.issn
1949-2553
dc.identifier.uri
dc.description.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
dc.format.extent
5 p.
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Impact Journals
dc.relation.isformatof
Reproducció digital del document publicat a: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1965
dc.relation.ispartof
Oncotarget, 2014, vol. 5, núm. 9, p. 2344-2348
dc.rights
Reconeixement 3.0 Espanya
dc.rights.uri
dc.source
Menéndez, Javier A. Quirantes-Piné, Rosa Rodríguez-Gallego, Esther Cufí, Sílvia Corominas-Faja, Bruna Cuyàs, Elisabet Bosch-Barrera, Joaquim Martin-Castillo, Begoña Segura-Carretero, Antonio Joven, Jorge 2014 Oncobiguanides: Paracelsus" law and nonconventional routes for administering diabetobiguanides for cancer treatment Oncotarget 5 9 2344 2348
dc.title
Oncobiguanides: Paracelsus' law and nonconventional routes for administering diabetobiguanides for cancer treatment
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.idgrec
021160