Cell States in Cancer: Drivers, Passengers, and Trailers.

ABSTRACT

SUMMARY: Cancer is traditionally perceived through a genetic lens, with therapeutic strategies targeting oncogenic driver mutations. We advocate an overarching framework recognizing tumors as comprising driver, passenger, and trailer cell states Tailoring therapies to simultaneously target driver genetics and cell states may enhance effectiveness and durability. SIGNIFICANCE: We redefine cancer progression by introducing a model that categorizes tumor cells into "driver," "passenger," and "trailer" phenotypes, expanding the focus on genetic aberrations to cellular behavior. This approach offers a roadmap to guide refining therapeutic strategies for more precise and durable cancer treatments that address tumor heterogeneity and plasticity.