1. Genetic Mutations: Accumulation of random mutations during cell division can lead to genetic diversity. 2. Epigenetic Changes: Modifications that affect gene expression without altering the DNA sequence contribute to heterogeneity. 3. Tumor Microenvironment: Variations in the surrounding stroma, immune cells, and blood supply can influence cancer cell behavior. 4. Clonal Evolution: Over time, different cancer cell clones can evolve and dominate the tumor landscape.