title: Attacking the supply wagons to starve cancer cells to death.
abstract: The constitutive anabolism of cancer cells not only supports proliferation but also addicts tumor cells to a steady influx of exogenous nutrients. Limiting access to metabolic substrates could be an effective and selective means to block cancer growth. In this review, we define the pathways by which cancer cells acquire the raw materials for anabolism, highlight the actionable proteins in each pathway, and discuss the status of therapeutic interventions that disrupt nutrient acquisition. Critical open questions to be answered before apical metabolic inhibitors can be successfully and safely deployed in the clinic are also outlined. In summary, recent studies provide strong support that substrate limitation is a powerful therapeutic strategy to effectively, and safely, starve cancer cells to death.
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, CA, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Selwan
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, CA, USA.
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Finicle
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, CA, USA.
authors.forename: Seong M
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, CA, USA.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Edinger
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D031204:Caloric Restriction / Q000009:adverse effects; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000009:adverse effects / Q000627:therapeutic use; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010873:Pinocytosis / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D049990:Membrane Transport Modulators; D009363:Neoplasm Proteins
keywords: autophagy; cancer; macropinocytosis; metabolism; nutrient transporter; sphingolipid