Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine.

2.50
Hdl Handle:
http://hdl.handle.net/10033/121102
Title:
Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine.
Authors:
Philippi, C; Loretz, B; Schaefer, U F; Lehr, C M
Abstract:
Telomerase as an enzyme is responsible for the renewal of the chromosomal ends, the so-called telomeres. By preventing them from shortening with each cell cycle, telomerase is able to inhibit cellular senescence and apoptosis. Telomerase activity, which is detectable in the majority of cancer cells, allows them to maintain their proliferative capacity. The thus obtained immortality of those cells again is a key to their malignancy. Based on these discoveries, it is obvious that telomerase inhibitors would represent an innovative approach to fight cancer, and a variety of such candidate molecules are currently in the pipeline. Telomerase inhibitors largely fall in two classes of compounds: small synthetic molecules and nucleotide-based biologicals. For several candidates, some proof of concept studies have been demonstrated, either on cell cultures or in animal models. But the same studies also revealed that inefficient delivery is largely limiting the translational step into the clinic. The most appealing feature of telomerase inhibitors, which distinguishes them from conventional anticancer drugs, is probably seen in their intrinsic non-toxicity to normal cells. Nevertheless, efficient delivery to the target cells, i.e. to the tumor, is still required. Here, some well-known biopharmaceutical problems such as insufficient solubility, permeability or even metabolic stability are frequently encountered. To address these challenges, there is a clear need for adequate delivery technologies, for example by using nanomedicines, that would allow to overcome their biopharmaceutical shortcomings and to warrant a sufficient bioavailability at the target side. This review first briefly explains the concept of telomerase and telomerase inhibition in cancer therapy. It secondly aims to provide an overview of the different currently known telomerase inhibitors. Finally, the biopharmaceutical limitations of these molecules are discussed as well as the possibilities to overcome those limits by novel drug carrier systems and formulation approaches.
Affiliation:
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
Citation:
Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine. 2010, 146 (2):228-40 J Control Release
Journal:
Journal of controlled release : official journal of the Controlled Release Society
Issue Date:
1-Sep-2010
URI:
http://hdl.handle.net/10033/121102
DOI:
10.1016/j.jconrel.2010.03.025
PubMed ID:
20381558
Type:
article
Language:
en
ISSN:
1873-4995
Appears in Collections:
publications of the department drug delivery ([TC] DDEL)

Full metadata record

DC FieldValue Language
dc.contributor.authorPhilippi, Cen
dc.contributor.authorLoretz, Ben
dc.contributor.authorSchaefer, U Fen
dc.contributor.authorLehr, C Men
dc.date.accessioned2011-02-03T12:41:35Zen
dc.date.available2011-02-03T12:41:35Zen
dc.date.issued2010-09-01en
dc.identifier.citationTelomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine. 2010, 146 (2):228-40 J Control Releaseen
dc.identifier.issn1873-4995en
dc.identifier.pmid20381558en
dc.identifier.doi10.1016/j.jconrel.2010.03.025en
dc.identifier.urihttp://hdl.handle.net/10033/121102en
dc.description.abstractTelomerase as an enzyme is responsible for the renewal of the chromosomal ends, the so-called telomeres. By preventing them from shortening with each cell cycle, telomerase is able to inhibit cellular senescence and apoptosis. Telomerase activity, which is detectable in the majority of cancer cells, allows them to maintain their proliferative capacity. The thus obtained immortality of those cells again is a key to their malignancy. Based on these discoveries, it is obvious that telomerase inhibitors would represent an innovative approach to fight cancer, and a variety of such candidate molecules are currently in the pipeline. Telomerase inhibitors largely fall in two classes of compounds: small synthetic molecules and nucleotide-based biologicals. For several candidates, some proof of concept studies have been demonstrated, either on cell cultures or in animal models. But the same studies also revealed that inefficient delivery is largely limiting the translational step into the clinic. The most appealing feature of telomerase inhibitors, which distinguishes them from conventional anticancer drugs, is probably seen in their intrinsic non-toxicity to normal cells. Nevertheless, efficient delivery to the target cells, i.e. to the tumor, is still required. Here, some well-known biopharmaceutical problems such as insufficient solubility, permeability or even metabolic stability are frequently encountered. To address these challenges, there is a clear need for adequate delivery technologies, for example by using nanomedicines, that would allow to overcome their biopharmaceutical shortcomings and to warrant a sufficient bioavailability at the target side. This review first briefly explains the concept of telomerase and telomerase inhibition in cancer therapy. It secondly aims to provide an overview of the different currently known telomerase inhibitors. Finally, the biopharmaceutical limitations of these molecules are discussed as well as the possibilities to overcome those limits by novel drug carrier systems and formulation approaches.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntineoplastic Agentsen
dc.subject.meshDrug Delivery Systemsen
dc.subject.meshEnzyme Inhibitorsen
dc.subject.meshHumansen
dc.subject.meshNanomedicineen
dc.subject.meshNeoplasmsen
dc.subject.meshTelomeraseen
dc.titleTelomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine.en
dc.typearticleen
dc.contributor.departmentDepartment of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.en
dc.identifier.journalJournal of controlled release : official journal of the Controlled Release Societyen

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