Lineage Plasticity in Cancer: How Tumors Change Identity and Resist Therapy

Cancer is not always biologically fixed. As tumors evolve, some cancer cells can change their identity, adopt new cellular states, and become less dependent on the pathways that originally defined them.

This process, known as lineage plasticity in cancer, is emerging as an important explanation for why some tumors behave differently over time and why treatment resistance can develop even without a new dominant mutation. Instead of simply becoming stronger versions of the same cancer, some tumor cells can reprogram themselves and take on a different biological state.

Understanding how cancer cells change identity is opening a new way of thinking about tumor evolution, treatment resistance, and the limits of therapies that target a single pathway. It also raises an important question: how much of cancer resistance is driven not by new mutations, but by the ability of tumor cells to become something different?