Live-cell imaging demonstrates that a subset of neuroblastoma cells evades chemotherapy-induced death if they are in early G1 phase of the cell cycle at the time of drug treatment and have sufficiently high levels of MYCN.
Chemotherapy remains the first line of treatment for most cancers. However, tumors often become refractory to these treatments, referred to as chemoresistance. Resistance and relapse are generally attributed to heterogeneity in drug response, wherein a subset of cells are less susceptible to the drug, giving rise to tumor regrowth. While it is now appreciated that both genetic and nongenetic modes contribute to resistance (Brock et al., 2009), including cellcycle position and slow-cycling kinetics (Kreso and Dick, 2014), few papers have directly investigated the link between cell-cycle stage at the time of drug treatment and cell fate after treatment. In this issue of Cell Systems, Ryl et al. focus on this problem and elucidate the cellular basis of chemoresistance in MYCN-overexpressing neuroblastoma cells by analyzing single-cell responses to the chemotherapeutic agent, doxorubicin.