“…In these common workflows, one tumor block is chosen to serve as a representative sample for molecular analyses and decision-making [2,12,13]. Despite the significant contributions these profiling approaches have made towards furthering the understanding of cancer biology and personalized clinical interventions, these profiling techniques often fail to translate into durable, life-prolonging cancer treatments [2,3,12,14]. A widely supported explanation for this phenomenon is the influence of diverse intratumoral subpopulations with differing therapeutic resistances, with multiple studies across cancer types implicating heterogeneous intratumoral biology in cancer treatment failure and poor patient outcomes (Figure 2) [2,12,13,15,16].…”