Volume 22 Issue 3, March 2023

Clinic-ready inhibitors, degraders and molecular glues are pushing cancer frontiers by targeting KRAS variants including KRAS-G12D.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons. In their Review, Shaw and colleagues provide a comprehensive picture of the various pathological mechanisms involved in this complex disease, and discuss the deep and diverse pipeline under development to tackle these processes. They highlight advances in ALS translational research that might be broadly applicable to other neurodegenerative disorders.

Single-agent therapies targeting specific dysregulated pathways in cancer can be highly effective, but drug resistance frequently develops. Here, Bernards and colleagues discuss the mechanisms underlying resistance to targeted therapies, and assess how these can be suppressed by using tailored combination therapies.

Bayesian statistical approaches that explicitly incorporate existing data into clinical trial design, analysis and decision-making have the potential to substantially reduce the time and cost of bringing new medicines to patients in some contexts, but remain underused. This Perspective highlights the value of Bayesian methods in drug development, discusses barriers to their application and recommends approaches to address them.