Cancer Metabolism

Cancer cells reprogram metabolism to support survival, growth, and adaptation under stress. Although increased glucose utilization has been recognized for more than a century, mitochondria are now understood to play a central role in cancer biology by coordinating energy production, biosynthetic demand, redox balance, stress responses, and interactions between tumor cells and their microenvironment. 

Madera’s approach is distinct from conventional cytotoxic agents and from therapies that primarily inhibit oncogenic signaling pathways. Instead, Madera targets a major support system that cancer cells rely on to survive and grow. Because many cancer cells already operate under heightened metabolic and proteotoxic stress, they may have less flexibility than normal cells to tolerate additional disruption of mitochondrial function. 

Madera is developing novel small-molecule ClpP agonists that directly activate a mitochondrial protease, disrupting mitochondrial function and selectively impairing the survival machinery of difficult-to-treat tumors.