Figure 2

Co-evolution of tumor (primary versus recurrent) with therapeutic-modified microenvironment in-patient in parallel with an ex vivo engineered tissue graft cultured tumor for time-dependent changes. MRI images show that tumor diagnostics, resection, recurrence and yet another resection of a young female glioblastoma patient during treatment of surgery, radiation, and chemotherapy. (Yellow arrows: Tumor mass). A: pre-operation (post-biopsy), axial view showing diagnostics, and appearance of the tumor. B: Immediate postsurgery, axial view showing removal of the tumor. C: 3-month post-surgery, axial view showing recurrence of the tumor. D: 4-month post-surgery, axial view showing the growth of the recurrent tumor. E: second post-surgery and gamma knife, axial view showing removal of the tumor. Note that the genome sequence (a) obtained from the primary tumor (A) is compared with the genome sequence (d) obtained from the recurrent tumor (D) to determine the genetic mutations evolved under the therapeutic pressure. The genome sequence (d) obtained from the recurrent tumor (D) is compared with the genome sequence (c) derived from an ex vivo engineered tissue graft [91],[99]-cultured tumor (b) to determine if the ex vivo models the genetic and epigenetic changes in-patient. Such a correlation, if established, can be used to predict the therapeutic-driven changes of intratumor spatial and temporal genetic and epigenetic information. Note that a mouse-derived ex vivo model may be replaced by using a patient-specific engineered tissue graft to screen for personalized treatment.