Figure 3.

Developmental biology of cancer cells. (A) Cancer cell-of-origin (or cancer-initiating cell): the cell where the first genetic lesion linked to the development of the tumour takes place. It might be located anywhere within the physiological differentiation pathway. It does not need to have any phenotypic relationship with the final phenotype of the tumour cells (either stem or differentiated). (B) CSC (cancer-maintaining cell): those cells that have the capacity to regenerate all the cellular diversity of the tumour. They retain broad self-renewal potential and differentiation potential. They arise initially from the cancer cell-of-origin, and then they can self-propagate. (C) Tumoural reprogramming: the process by which the initial oncogenic lesion(s) can ‘reset’ the epigenetic and/or transcriptome status of an initially healthy cell (the cancer cell-of-origin), therefore establishing a new, pathological differentiation program ultimately leading to cancer development, where the oncogenic lesion(s) does not need to be present anymore once the initial cancer fate-inducing change has taken place.