Fig. 1.

Tumor development and evolution under hypoxic conditions. Cancer starts as a single cell that acquires genetic mutations that promote rapid, uncontrolled growth. When the tumor reaches 1 to 2 mm in diameter, oxygen and nutrient supply by diffusion from nearby blood vessels is insufficient to maintain cancer cell growth. In order to sustain growth and survival under these low-oxygen conditions, the cancer cells modify their genome and epigenome via clonal evolution to generate a diversity of cancer cells with distinct properties. At this late stage, cancer cells may spread to other parts of the body and become resistant to both radio- and chemotherapy.