Abstract
Aberrant metabolism is a major hallmark of cancer. Abnormal cancer metabolism, such as aerobic glycolysis and increased anabolic pathways, has important roles in tumorigenesis, metastasis, drug resistance, and cancer stem cells. Well-known oncogenic signaling pathways, such as phosphoinositide 3-kinase (PI3K)/AKT, Myc, and Hippo pathway, mediate metabolic gene expression and increase metabolic enzyme activities. Vice versa, deregulated metabolic pathways contribute to defects in cellular signal transduction pathways, which in turn provide energy, building blocks, and redox potentials for unrestrained cancer cell proliferation. Studies and clinical trials are being performed that focus on the inhibition of metabolic enzymes by small molecules or dietary interventions (e.g., fasting, calorie restriction, and intermittent fasting). Similar to genetic heterogeneity, the metabolic phenotypes of cancers are highly heterogeneous. This heterogeneity results from diverse cues in the tumor microenvironment and genetic mutations. Hence, overcoming metabolic plasticity is an important goal of modern cancer therapeutics. This review highlights recent findings on the metabolic phenotypes of cancer and elucidates the interactions between signal transduction pathways and metabolic pathways. We also provide novel rationales for designing the next-generation cancer metabolism drugs.
Highlights
Uncontrolled, infinite proliferation is an essential characteristic of tumors
Glutamine is critical for cancer cell proliferation because nitrogen is an essential metabolite for nucleotide biosynthesis and glutamine is a precursor for synthesis of other non-essential amino acids (NEAAs) and fatty acids [33] (Figure 1)
Myc regulates expression of genes associated with glucose, glutamine, and fatty acid metabolism
Summary
Recent studies highlight the differences in metabolic processes between cancer cells and their normal counterparts. Instead, they obtain ATP through glycolysis [1]. Tumors arise by mutations within oncogenes and tumor suppressor genes These genetic mutations directly regulate the expression and activity of metabolic enzymes. The abnormal metabolism of cancer cells is not merely a genetic mutation phenotype. It directly affects tumor signal transduction pathways and cellular reactions. Based on this concept, the next-generation anticancer therapeutics examined in many studies and clinical trials target cancer-specific metabolic phenotypes. By analyzing interactions between metabolism and signaling pathways, we aim to establish potential therapeutic targets for new metabolism-based anticancer drugs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
