Abstract
ABSTRACTCarbonic anhydrase IX (CA IX) is an enzyme overexpressed in many hypoxic tumors as a consequence of hypoxia inducible factor 1α (HIF-1α) transcription factor cascade. CA IX is a highly active catalyst for the conversion of CO2 to bicarbonate and protons, being involved in pH regulation, but also contributes to the acquisition of metastasic phenotypes and to chemoresistance with some widely used anticancer drugs. CA IX inhibition with small molecules or antibodies has profound antitumor/antimetastatic effects, and also depletes the number of cancer stem cells within the hypoxic niche, all factors crucial for new generation anticancer agents. The present patent proposes a CA IX score, which considers both the staining intensity as well as the percentage of cells stained at a specific range of intensities, conventionally taken between 0 (no staining) and 3 (very strong staining). Based on the CA IX score, it was proposed that only patients with the score in the range of 2.0 – 2.6 should be given antitumor therapies comprising CA IX inhibitors such as the monoclonal antibody girentuximab or small molecule inhibitors.
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