Fig. 6
The tissue multi-compartment model of cancer treatment. a The biomarker data show that Tie2 is a tumor response biomarker for VEGFi and that the predictive value of vascular biomarker data adds to epithelial biomarker data to improve modeling of progressive disease. Together with our previous data in ovarian cancer, the implication of these findings is that the vascular and epithelial compartments are distinct, valid and useful concepts in the treatment of each recurrence of solid tumors. Examples of individual patient data are shown in b–e; the x-axis represents the number of days that the patient received treatment until they developed RECIST-defined progression (i.e., total tumor burden), Tie2 data are shown as solid black lines and CK18 in dotted black lines. The units for both biomarkers are pg/ml. In b Patient 32 has undergone an epithelial response, vascular response, epithelial progression, and vascular progression. In c, the patient had an epithelial response but not a vascular response thus the patient could have stopped bevacizumab after ~8 weeks of treatment. The patient subsequently had epithelial and vascular progression. In d the patient had an epithelial and vascular biomarker response and then developed vascular progression but not epithelial biomarker progression. In e the patient attained an epithelial and vascular response with subsequent epithelial progression but not vascular progression, suggesting that the vasculature was still controlled at the point of RECIST progression. CK18; cytokeratin 18, VEGFi; vascular endothelial growth factor inhibitor, RECIST; response evaluation criteria in solid tumors
