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Figure 2. Centrosome amplification leads to tumor initiation and cancer progression through intra-tumor heterogeneity. Two models are described above. First, centrosome amplification leads to pseudobipolar spindles that culminate in chromosome instability and aneuploidy. Second, centrosome amplification leads to defects in cytokinesis that culminates in chromosome instability and tetraploidy. Both mechanisms converge to initiate cancer. Cancer progression and chemoresistance occurs and is maintained as a consequence of intra-tumor heterogeneity. Chromosome instability inhibitors (e.g., AURKs, Mps1, and PLKs) are therapeutic targets that may prevent this chain of events by targeting early steps of this process