CA9 and neoplasm: Currently, hypoxic-tumor targeted therapies fall into four major categories: 1) Hypoxia-activated prodrugs that can kill tumor cells in hypoxic zones, 2) Molecules that inhibit HIF thereby abrogating HIF-downstream signaling, 3) Therapies that increase tumor oxygenation and 4) Drugs that modulate hypoxia-associated TME remodeling such as acidosis (e.g. CAIX) (15, 63, 65).