Abstract
Cancer is a systemic disease that involves malignant cell-intrinsic and -extrinsic metabolic adaptations. Most studies have tended to focus on elucidating the metabolic vulnerabilities in the primary tumor microenvironment, leaving the metastatic microenvironment less explored. In this opinion article, we discuss the current understanding of the metabolic crosstalk between the cancer cells and the tumor microenvironment, both at local and systemic levels. We explore the possible influence of the primary tumor secretome to metabolically and epigenetically rewire the nonmalignant distant organs during prometastatic niche formation and successful metastatic colonization by the cancer cells. In an attempt to understand the process of prometastatic niche formation, we have speculated how cancer may hijack the inherent regenerative propensity of tissue parenchyma during metastatic colonization.