Intratumor heterogeneity describes phenomena that cancer cells from a single focal population can be highly diverse in morphology, gene expression, metabolism, motility, proliferation, metastatic potential, and drug sensitivity (McGranahan and Swanton, 2017). The heterogeneity is the consequence of cancer evolution and the major cause of therapeutic failure due to drug resistance (McGranahan and Swanton, 2017). Theoretically, multi-target combination therapy may eliminate heterogeneous cancer cells but may also induce severe side effects and promote the genesis of novel malignancy. Therefore, further investigations on the pattern and mechanism of cancer heterogeneity are required, with the hope to better refine the treatment strategies. However, there is lack of appropriate in vivo cancer models for simulating multidimensional heterogeneity. Patient/cell-derived tumor xenografts (P/CDX) and spontaneous models induced by toxic substances are naturally heterogeneous in cellular composition during the time but are also highly personalized or unrepeatable. By contrast, transgenic cancer models provide definite genetic backgrounds via direct manipulation of oncogenic pathways; however, the tissue-specific modifications are usually on the whole organ level and poorly mimic the focal lesion(s) in the real cancer patients.