Table of contents
December 2008 Vol 7 No 12
In this issue
p957 | doi:10.1038/nrd2763
Editorial: Apoptosis: a clinical perspective
p959 | doi:10.1038/nrd2756
News and Analysis
End of the line for cannabinoid receptor 1 as an anti-obesity target? | PDF (444 KB)
p961 | doi:10.1038/nrd2775
News Feature
Anticipating REMS | PDF (256 KB)
p963 | doi:10.1038/nrd2776
News in Brief
JUPITER highlights anti-inflammatory effects of statin treatment | Novartis acquires Nektar's pulmonary drug delivery business | FDA discusses Alzheimer's disease biomarkers | EMEA takes hard stance in Crohn's disease trials | Priority review voucher draft guidance available | PDF (416 KB)
p964 | doi:10.1038/nrd2777
Biobusiness Briefs
Trial watch : Progress for Phase III cancer vaccines | PDF (171 KB)
p966 | doi:10.1038/nrd2766
Regulatory watch : First drug for idiopathic pulmonary fibrosis approved in Japan | PDF (142 KB)
p966 | doi:10.1038/nrd2767
Market Watch : Pharma industry strategic performance: 2007–2012E | PDF (152 KB)
p967 | doi:10.1038/nrd2768
Patent watch
An Audience With
Daphne Zohar | PDF (169 KB)
p970 | doi:10.1038/nrd2779
The founder of PureTech Ventures discusses the firm's unique approach to company creation.
From the analyst's couch
Targeting apoptosis: selected anticancer strategies | PDF (249 KB)
p971 | doi:10.1038/nrd2662
Fresh from the Pipeline
Lacosamide | PDF (248 KB)
p973 | doi:10.1038/nrd2764
Research Highlights
Protein–protein Interactions: Getting rid of JNK | PDF (238 KB)
p975 | doi:10.1038/nrd2771
Type 1 diabetes: Islet renovation | PDF (224 KB)
p976 | doi:10.1038/nrd2769
G-protein-coupled receptors: A novel double act | PDF (141 KB)
p976 | doi:10.1038/nrd2770
Apoptosis: New strategies to tip the BCL-2 balance | PDF (177 KB)
p977 | doi:10.1038/nrd2773
Obesity: Repurposed agent shows weight-loss potential | PDF (219 KB)
p978 | doi:10.1038/nrd2772
In brief
Antibacterial drugs | G-protein-coupled receptors | Analgesia | Renal disease | PDF (141 KB)
p978 | doi:10.1038/nrd2774
Focus on: Apoptosis
Perspective
Opinion
The genetics of the p53 pathway, apoptosis and cancer therapy
Alexei Vazquez, Elisabeth E. Bond, Arnold J. Levine & Gareth L. Bond
p979 | doi:10.1038/nrd2656
The p53 tumour suppressor pathway is an attractive target for the development of anticancer therapies. This Perspective highlights recent progress with agents that modulate components of the p53 pathway — in particular, p53 itself and its negative regulator MDM2 — focusing on how studies of their genetic variations, including mutations in cancer cells and inherited polymorphisms, could help tailor the use of existing agents and aid the development of novel drugs.
Reviews
BCL-2 family antagonists for cancer therapy
Guillaume Lessene, Peter E. Czabotar & Peter M. Colman
p989 | doi:10.1038/nrd2658
The pro-survival BCL-2 family of proteins provides exciting drug targets for the selective induction of apoptosis in cancer cells, in which these proteins are often overexpressed. Lessene and colleagues review the preclinical and clinical data for BCL-2 antagonists, and recommend criteria for establishing the mode of action for this new drug class.
Directing cancer cells to self-destruct with pro-apoptotic receptor agonists
Avi Ashkenazi
p1001 | doi:10.1038/nrd2637
Pro-apoptotic receptor agonists have a remarkable ability to selectively induce apoptosis in a wide spectrum of malignant cells. Ashkenazi discusses the scientific rationale, emerging clinical data and future potential for this exciting new class of anti-cancer drugs.
Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities
Inki Kim, Wenjie Xu & John C. Reed
p1013 | doi:10.1038/nrd2755
Endoplasmic reticulum (ER) stress is induced following the accumulation of unfolded proteins in the ER. This triggers the unfolded protein response, which initially acts to compensate for damage, but if prolonged or excessive can trigger cell death. Here, Reed and colleagues discuss the role of ER-initiated cell death pathways in diseases including neurodegeneration, hypoxia, heart disease, diabetes and immune disorders, while identifying promising therapeutic targets.
Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-
B pathways
Anwesha Dey, Vinay Tergaonkar & David P. Lane
p1031 | doi:10.1038/nrd2759
Apoptosis can be induced by activating/stabilizing p53, and by inhibiting NF-
B. Now, it has been found that a surprising number of small molecules can do both. This article describes the principles behind such dual activity, discusses current candidate molecules and provides an outlook to their future development as anticancer drugs.
