A major barrier to cancer therapy is the emergence of drug-tolerant states that allow tumor cells to bypass the targeted pathway. These refractory states arise through reversible cellular plasticity, a process that also occurs during development and regeneration, giving rise to new lineages or phenotypes and restoring drug sensitivity upon treatment withdrawal. Over time, genetic mutations may accumulate, leading to permanent resistance. This paradigm expands the focus from targeting genetic mechanisms alone to also exploiting nongenetic vulnerabilities, driving clinical strategies that prevent or eliminate plastic and transformed populations. Here, we provide an overview of nongenetic plasticity mechanisms and their emerging clinical applications. de Sauvage and colleagues discuss the latest advances in therapy-driven cancer plasticity processes and how this knowledge might be applied to clinical strategies.
The impact of earlier brain insults on the glioblastoma microenvironment is poorly understood. A study now shows that prior stroke alters astrocytes to promote glioblastoma growth and invasion via downregulation of calcium signaling.
