Oncogenic competence: balancing mutations, cellular state, and microenvironment.

Cancer development is driven by mutations, yet tumor-causing mutations only lead to tumor formation within specific cellular contexts. The reasons why certain mutations trigger malignant transformation in some contexts but not others remain often unclear. Both intrinsic and extrinsic factors play a key role in driving carcinogenesis by leading the cells toward a state of 'oncogenic competence'. This state is shaped by the transcriptional and epigenetic programs that define a specific cell in time and space. These programs arise from the interplay between genetic mutations, cellular lineage, differentiation state, and microenvironment. A deeper understanding of oncogenic competence is essential to uncover the mechanisms behind tumor initiation and, ultimately, advance the development of novel targeted therapies for cancer treatment and prevention.