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. 2015 Jul 28;7:225–239. doi: 10.2147/CMAR.S47797

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© 2015 Kim. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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Schematic illustration of tumorigenesis.

Notes: Normal cells accumulate mutations in 2–8 cancer-driving genes and form primary tumors. Primary tumors accumulate additional genetic alterations and progress to metastatic tumors. Intra-tumor heterogeneity is already present in primary tumors. Tumor cells disseminate into the blood stream during early stages in tumorigenesis. Genetic heterogeneity is present between metastases as each metastatic clone evolves independent of one another. Time frame for currently available targeted therapy is marked with blue arrow: Adjuvant therapy for breast cancer and clinical trials for metastatic cancer. Proposed time window for combined targeted and immune therapy is marked with black arrow.