The safety windows and toxicity of clinically available known drugs allow drug repurposing to be a popular treatment strategy for several diseases, including cancers. Several common drugs, e.g., metformin, statin, and aspirin are on clinical trials for repurposing in oncology treatment. Most of repurposed drugs, however, cannot be used as single agents and some do not exert any clinically significant effects. The limitations and possible biases from observational studies and preclinical models to repurpose these drugs are debatable. In this article, the limitations and probability of using metformin, one of the most repurposed drugs for cancer treatment and in oncological practice, are discussed.

Background: Cancer remains a global health challenge, characterized not just by uncontrolled cell proliferation but also by the complex metabolic reprogramming that underlies its development and progression. Objectives: This review delves into the intricate relationship between cancer and its metabolic alterations, drawing an innovative comparison with the cosmological concepts of dark matter and dark energy to highlight the pivotal yet often overlooked role of metabolic reprogramming in tumor evolution. Methods: It scrutinizes the Warburg effect and other metabolic adaptations, such as shifts in lipid synthesis, amino acid turnover, and mitochondrial function, driven by mutations in key regulatory genes. Results: This review emphasizes the significance of targeting these metabolic pathways for therapeutic intervention, outlining the potential to disrupt cancer’s energy supply and signaling mechanisms. It calls for an interdisciplinary research approach to fully understand and exploit the intricacies of cancer metabolism, pointing toward metabolic reprogramming as a promising frontier for developing more effective cancer treatments. Conclusion: By equating cancer’s metabolic complexity with the enigmatic nature of dark matter and energy, this review underscores the critical need for innovative strategies in oncology, highlighting the importance of unveiling and targeting the “dark energy” within cancer cells to revolutionize future therapy and research.