Giant cancer study reveals effectiveness of 'off label' treatments

This episode of The Nature Podcast explores two major scientific studies. First, a landmark 10-year Dutch cancer trial known as the Drug Rediscovery Protocol, which evaluated the effectiveness of off-label cancer treatments—drugs used for cancers different from those they were approved to treat. Led by oncologist Emil Wust, the trial analyzed over 610 patients with advanced solid tumors, finding that about one-third showed tumor stabilization or partial regression for at least four months, and 7% experienced long-term responses, some potentially curative. However, the results were sobering: 93% of patients saw little to no benefit, underscoring the limitations of off-label use despite its potential. The study highlights the need for better data-sharing infrastructure, especially for rare cancers, and has already influenced Dutch healthcare policy and inspired similar trials globally. The second story examines human evolution through a massive ancient genome study of over 10,000 individuals from Western Eurasia, revealing strong evidence of directional selection in the human genome over the past 10,000 years—particularly in genes related to immunity, metabolism, and disease risk. While the findings suggest rapid adaptation to farming, population density, and disease, researchers caution against overinterpreting complex traits like intelligence or mental health, emphasizing that modern genetic predictors don’t reflect ancient traits directly. The study is a major resource, but its methodology and conclusions remain debated. Key takeaways include: 1) Off-label cancer treatments can help a small but meaningful subset of patients, especially those with rare cancers, but must be used cautiously due to limited efficacy and side effects; 2) A robust, data-driven infrastructure for off-label treatment is essential to avoid repeating ineffective therapies; 3) Human evolution has been more dynamic than previously thought, with strong natural selection acting on immune and metabolic genes in recent millennia; 4) Caution is needed when linking ancient genetic changes to modern complex traits like intelligence or mental illness; 5) The study’s methodology, while innovative, requires scrutiny to distinguish true selection from population shifts and genetic drift.