NaPi2b (sodium-dependent phosphate transporter, SLC34A2)

Class

NaPi2b-directed antibody-drug conjugate (topoisomerase I inhibitor payload)

NaPi2b, encoded by the gene SLC34A2, is a transporter protein that moves phosphate ions across cell membranes using the energy of a sodium gradient. It is normally found on the surface of certain epithelial cells, including those lining the lungs and reproductive tract, where it helps regulate phosphate balance. In several cancers, particularly ovarian carcinoma and a subset of non-small cell lung cancers, NaPi2b is present at markedly higher levels on the tumor cell surface than on most healthy tissue. This selective overexpression makes it an attractive docking point for antibody-drug conjugates (ADCs), a modality that pairs a targeting antibody with a potent cytotoxic payload. The antibody component recognizes NaPi2b, allowing the conjugate to concentrate at tumor cells before releasing a topoisomerase I inhibitor, a class of agent that damages DNA replication machinery and drives cell death. Because the antibody restricts most of the cytotoxic exposure to cells bearing the target, this approach aims to achieve tumor-selective killing while limiting the systemic toxicity typically associated with conventional chemotherapy. The broader rationale for pursuing NaPi2b-directed therapy rests on the combination of a validated tumor-surface marker with a payload class known for potent activity against cancer cells with varying proliferation rates, extending the reach of the treatment beyond only rapidly dividing cells.