Clonal dynamics and therapeutic response. While we can see 4 general types of response to therapy in the clinic (top panel, nonresponse, early relapse, late relapse, and long-term response), the hypothesized underlying intratumoral views (bottom panel) of these scenarios could have significant implications for therapy. If the response of patients to therapeutic intervention is either a long-term response or complete nonresponse, we hypothesize that the underlying genetic diversity is minimal, with clones either homogenously sensitive or homogenously resistant to therapy. Those that initially respond to therapy but relapse early or late after therapy is completed could be examples of either selection for the fittest existing clone (early relapsers, survival of the fittest) or the emergence of new clones generated during (or by) therapy that over time cause another outgrowth of the tumor (late relapsers, secondary clonal evolution). To distinguish which of the evolutionary pressures (resistance, sensitivity, survival of the fittest, or secondary clonal evolution) apply to each clinical manifestation requires additional tools suitable for clinical monitoring of clonal diversity and clonal identities. (Figure by Dr. Amy Paguirigan).