Cancer Metabolism and Aggressive Tumor Behavior

Aggressive tumor behavior poses a serious threat to the success of cancer therapy. Altered cancer metabolism is a hallmark feature of tumor initiation, progression, and metastases. During these processes, the tumor cells suffer bioenergetic and nutrient demand, which is met by metabolic reprogramming or preferential nutrient usage facilitated by the acquisition of driver oncogenic mutations and inactivation of tumor-suppressor genes. The metabolic heterogeneity and plasticity of tumor cells provide cellular fitness and survival advantage in the harsh tumor microenvironment (TME), resulting in aggressive tumor growth and resistance to chemotherapies. Besides, other cell types, including stroma, immune cells, and extracellular matrix in the TME, undergo metabolic switching that influences disease progression. Because aberrant glucose metabolism is central to tumor cell metabolic reprogram, various clinical trials targeting glucose uptake and its metabolites in combination with other molecular targets have been focused on reducing tumor progression by inhibiting the metabolic interplay. Here, we describe in detail how the metabolic plasticity of cancer cells and TME results in tumor progression and aggressiveness. In addition, we highlight the current approaches being explored for therapeutic intervention. This overview will help in understanding the intricated metabolic networks and open new avenues of cancer treatment.