The tumor macroenvironment as cancer metabolism's next frontier.

The deregulated utilization of nutrients by tumors, first observed over a century ago, is recognized as a hallmark of cancer and continues to be exploited clinically to image neoplastic disease. Despite this historic focus on cancer cells and, more recently, their neighbors, metabolic reprogramming is not limited to the tumor microenvironment. Tumors also have the capacity to rewire the metabolism of cells throughout the body, including those at distant sites, often referred to as the tumor macroenvironment. Alterations in the metabolism of noncancerous tissues outside the local tumor ecosystem are gaining attention, but their origins and consequences remain incompletely defined. A deeper understanding of these changes may reveal previously unrecognized signatures of disease and unexplored opportunities for therapeutic intervention.