Volume 21 Issue 2, February 2022

The FDA approved 50 novel drugs in 2021, including the first KRAS inhibitor for cancer and the first anti-amyloid antibody for Alzheimer’s disease.

Lack of predictive preclinical models is one of the reasons for the high rate of attrition in oncology drug development. This Review discusses the issues in preclinical-to-clinical translatability of molecularly targeted cancer therapies and the need to better align tumour biology in patients with preclinical model systems.

The unfolded protein response (UPR) aims to relieve endoplasmic reticulum (ER) stress and restore protein homeostasis, but also contributes to disease. Here, Marciniak et al. assess small molecules that target ER stress and the UPR, highlighting those diseases in which the role of the UPR and its therapeutic modulation have been most well studied.

Despite the link between metabolism and oncogenes, very few metabolism-based drugs for cancer have been successfully developed. This Review covers the setbacks and recent developments in targeting cancer metabolism, and discusses the path forward for the field.