New anti-cancer role for PDK1 inhibitors: preventing resistance to tamoxifen.
Tamoxifen is one of the most prescribed anti-breast-cancer drugs, but tumours becoming resistant hinder its efficacy in the clinic. There is therefore great interest in developing strategies to reduce resistance and sensitize breast cancer cells to tamoxifen. A groundbreaking study by Iorns et al. published in this issue of the Biochemical Journal suggests that a signal transduction pathway controlled by PDK1 (phosphoinositide-dependent kinase 1) plays a crucial role in regulating the sensitivity of breast cancer cells to tamoxifen. The implications of this study are that PDK1 or PI3K (phosphoinositide 3-kinase), Akt (also known as protein kinase B), S6K (S6 kinase) and mTOR (mammalian target of rapamycin) inhibitors, already being developed for cancer therapy, are likely to have additional utility in sensitizing breast tumours to tamoxifen. In this commentary we also discuss the possibility that inhibiting the PDK1 pathway may help overcome acquired resistance to other anti-cancer treatments.
Peifer
Christian
C
MRC Protein Phosphorylation Unit, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK.
Alessi
Dario R
DR
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004965:Estrogen Antagonists / Q000494:pharmacology; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology*
D004965:Estrogen Antagonists; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D013629:Tamoxifen; D017346:Protein Serine-Threonine Kinases