We propose here a new concept for designing drug therapy that will attempt to avoid the emergence of resitance by monitoring how each drug affects cell states at single cell resolution. We perform the study in context of the most common childhood cancer, acute lymphoblastic leukemia. Although the overall survival has improved over past decades, 10-15% of patients still encounter relapse that leads to a dramatic increase in cytotoxic burden, which endangers the development and life-long health of children. Our goal is to find new predictive and preventive measures to avoid disease recurrence.
Guided by a systems biology approach, we will carry out drug screens targeting B-cell vulnerabilities. A unique resource of primary patient samples will be utilized to study both in vivo and ex vivo treatment responses based on single cell omics and computational modeling. The results will be relevant in broader context of cancer therapy that suffers from prevalent emergence of resistance.