Carbonic Anhydrase IX (CAIX)

Class

CAIX-targeted radioligand therapy (68Ga/177Lu theranostic peptidomimetic)

Pathway

Hypoxia-induced transmembrane metalloprotease overexpressed in hypoxic solid tumors (e.g. CRC, ccRCC)

Carbonic Anhydrase IX (CAIX) is a zinc-containing enzyme anchored on the surface of certain cells, where it helps convert carbon dioxide and water into bicarbonate and protons. This activity helps cells manage the acidic, oxygen-poor conditions found in hypoxic (low-oxygen) tissue. CAIX production is controlled by hypoxia-inducible factor (HIF-1α), a protein that accumulates when oxygen is scarce. Many solid tumors outgrow their blood supply, creating hypoxic regions that switch on CAIX, while most normal tissues (with a few exceptions, such as parts of the digestive tract) keep it low. This selective, hypoxia-linked pattern makes CAIX a useful marker for locating tumor tissue. It is targeted in two complementary ways: monoclonal antibodies that bind its external region, and small radiolabeled peptide-like molecules that can be paired with different radioactive isotopes (one for imaging and one for treatment), a theranostic approach that allows visualization of CAIX-expressing tumor tissue before delivering a matched radiation-emitting therapy. This mechanism is especially relevant in clear cell renal cell carcinoma, where loss of a tumor-suppressor gene causes CAIX to be produced constantly regardless of oxygen levels, and in colorectal cancer, where hypoxic zones within the tumor drive its expression.