Genomics- and biomarkers-based tools for personalized treatment to reduce chemotherapy burden in pediatric leukemia

Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer in Europe, with approximately 4000 new cases per year. While standardized therapy has improved prognosis, challenges persist. Despite efforts to cure high-risk ALL patients, relapses occur amongst non-high-risk patients. Furthermore, as many as 50% of low-risk patients may benefit from a reduction in the duration of treatment.

This project aims to address the inadequate biological resolution of the current genetic risk stratification used for ALL treatment, paving the way for personalized treatment strategies.The project will be a transnational, multidisciplinary effort encompassing multi-omics studies in preclinical models, with milestones in biomarker identification, high throughput drug screens, and new therapeutic approaches.

Our specific aims include identifying circulating biomarkers to distinguish high-risk from low-to-intermediate-risk patients, enabling the shortening of chemotherapy for true low-risk patients, as well as targeted treatments for the genuine high-risk patient population.The significance of this project lies in its potential to reduce overtreatment and undertreatment in ALL, optimizing therapeutic outcomes for both low-risk and high-risk patients.

This effort will not only advance personalized treatment strategies for pediatric ALL, the developed analytical workflows will have applicability across a wide range of other diseases with a strong genetic basis.