The development of consensus taxonomy will be required to coordinate meaningful future research results. Furthermore, specific features to be addressed include establishing definitions to quantify necrosis, criteria for

tumor margin assessment, and quantifying the degree of enhancement and neovascularity. Once the key imaging features are clearly defined, the inter-observer variability for future radiogenomics research will need MK-2206 nmr to be reduced and structured reporting will be required to achieve reporting stability and consistency necessary for large-scale clinical studies. Theses biological and technical limitations are discussed further below. Increasing evidence supports the impact of intra-tumor genetic heterogeneity

on the metastatic ability of tumors and their resistance to therapeutic interventions. Genetic intra-tumoral heterogeneity may contribute to treatment failure by initiating phenotypic diversity that introduces tumor sampling bias and enables drug resistance to emerge [27], [28] and [29]. Recent massively parallel sequencing studies and epigenetic analysis of different tumor types have revealed that cancers are composed of mosaics of non-modal clones [30] and [31] which harbor distinct constellations of genomic alterations in addition to the founder genetic events, and that clonal selection occurs during metastatic progression [32] and [33]. Intra-tumor Arachidonate 15-lipoxygenase genetic heterogeneity, for example, may be present in high-grade serous ovarian cancer (HGSOC) [27], BYL719 cell line [28], [34], [35] and [36], resulting in incomplete response to

chemotherapy [34]. Using phylogenic tree analysis to evaluate relationships between tumor deposits in patients with ovarian cancer, Cowin et al. [34] found substantial copy number differences between metastatic deposits within individual patients and identified signaling pathways plausibly linked to peritoneal dissemination and establishment of metastatic foci. Significantly greater genomic change was observed in patients who experienced relapse after responding to chemotherapy than in patients who were resistant from the outset, possibly reflecting the requirement for selection of a subpopulation of resistant cells in cases initially sensitive to treatment [34]. Incorporating multiregional tumor analysis of both primary and metastatic disease into the development of new targeted therapies and validation of biomarkers of therapeutic response is therefore crucial; image-informed multiregional tumor analysis may be required to fully characterize tumor heterogeneity. Intra-tumor functional heterogeneity is often manifested by intermingled vascular compartments with distinct pharmacokinetic properties. DCE imaging provides a noninvasive method to evaluate tumor vasculature or metabolism rate based on contrast accumulation and washout.