I study drug resistance and subclonal heterogeneity in patient-derived xenografts. The clonal evolution of cancer plays a major role in therapy response and resistance. Some drugs may work only for a tumor subpopulation with specific genomic profiles (e.g.,somatic mutations or copy number alterations). Thus we need to track all tumor subpopulations to select a combination of drugs. The efficacy test of combination drugs requires biological models as similar as possible to human cancers. A patient-derived xenograft (PDX) system can be used, since tumors can be studied in animal models to observe the effect of pharmacologic agents with minimal noise factors.