Surviving the siege: A review on the metabolic hallmarks of cancer dormancy

Abstract

• This review synthesizes the evidence that defines metabolic reprogramming as an essential hallmark of this persistent state. • External cues from the tumor microenvironment, where stromal-immune signaling and resource competition dictate metabolic fate, critically shape these adaptive programs. • This review concludes that targeting these metabolic vulnerabilities is a highly promising strategy to forestall cancer recurrence. Cancer dormancy, a period of cellular hibernation, enables malignant cells to evade treatment and later initiate metastatic relapses, representing a central challenge in oncology. This review synthesizes the evidence that defines metabolic reprogramming as an essential hallmark of this persistent state. The authors find that dormant cells adopt a distinct bioenergetic identity, characterized by exceptional plasticity, which includes repurposed lipid pathways, a heightened capacity to neutralize oxidative stress, and a flexible reliance on both glycolytic and oxidative fuel sources. External cues from the tumor microenvironment (TME), where stromal-immune signaling and resource competition dictate metabolic fate, critically shape these adaptive programs. Although the specific metabolic profile can be heterogeneous and tissue-specific, the conserved reliance on certain pathways reveals a landscape of therapeutic liabilities. This review concludes that targeting these metabolic vulnerabilities is a highly promising strategy to forestall cancer recurrence. The path forward requires a focus on translating these findings through the clinical testing of metabolic modulators and the co-development of robust biomarkers to enable a new paradigm of personalized, preventive oncology.