Cancer stem cells as the relevant biomass for drug discovery.
The poor success rate of discovering new, effective chemotherapeutics for oncology may reflect the failure of targeting treatments to the more aggressive, tumorigenic cells of the malignancy. Data have now emerged from several laboratories, examining both liquid and solid primary tumor tissues, that implicate cancer stem cells (CSCs) as the 'master-driver' cellular population for tumorigenicity. Moreover, these putative CSCs appear relatively resistant to existing chemotherapeutic and radiation therapy. Several different cellular pathways have been identified as likely mechanisms causal for the underlying insensitivity of the CSCs to conventional therapy. Progress has been made in the isolation and expansion of these CSCs for constructing conventional high-throughput phenotypic screening campaigns. However, challenges remain in designing optimal proof-of-concept trials for the clinical development of compounds targeting the elimination of CSCs.
Winquist
Raymond J
RJ
Department of Pharmacology, Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, MA 02139, USA. raymond_winquist@vrtx.com
Furey
Brinley F
BF
Boucher
Diane M
DM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents