The potential of hyperpolarized (13)C MRI in assessing signaling pathways in cancer

Advances in genomics are enabling integration of various -omics to reveal the complexities underneath carcinogenesis. Multivariate signaling pathways are deregulated and evolve spatially and temporally depending on the tumor microenvironment. This finding shifts the focus of cancer research from "one disease-one target and drug" to "one disease-multiple pathway targets and combinational therapy" and imposes new challenges on the imaging community in terms of imaging targets, scales and information levels. In current clinical settings, most imaging modalities assess cancer risk through alternations in anatomy, function, metabolism, cellularity, or limited molecular events. Few clinical-translatable imaging modalities are capable of detecting aberrations in signaling pathways at the level of tissue biology. An exception to this is hyperpolarized (13)C magnetic resonance spectroscopic imaging (HP (13)C MRI), which is capable of imaging the molecular signatures of special metabolic enzymes using HP (13)C-labeled substrates. HP (13)C MRI can identify multiple metabolites including intermediates and products simultaneously to allow extraction of critical parameters such as flux alterations for multiple metabolic pathways. Meanwhile, recent progress in cancer metabolism research affirms that metabolic alterations are directly controlled by signaling pathways. Thus, in vivo assessment of aberrations occurring in signaling pathways becomes feasible through HP (13)C imaging. This report briefly reviews the connections between signaling pathways and cancer metabolic phenotypes, the current status of HP (13)C MRI in assessing signal pathways, and recent advances in HP (13)C MRI techniques. Integrated with cancer genomics and animal models, HP (13)C MRI may hold high promise in exploring important issues in cancer that are linked to functionality of signaling pathways. Examples include genomic-driven therapy, intratumoral heterogeneity, and drug resistances.