Tumor-specific cell-surface molecular targets

Tumor-specific cell-surface molecular targets represent a diverse group of proteins and carbohydrates expressed on the exterior of cancer cells that distinguish them from healthy cells (National Cancer Institute [NCI], 2024). These targets include tumor-specific antigens (TSAs), which are unique to malignant cells, and tumor-associated antigens (TAAs), which are overexpressed or abnormally presented on tumors (Scott et al., Nature Reviews Cancer, 2012). They are the primary focus of precision oncology, serving as the basis for monoclonal antibodies, antibody-drug conjugates (ADCs), and cellular therapies like CAR-T cells (Hafeez et al., Molecules, 2020). By binding to these surface markers, therapeutic agents can selectively inhibit oncogenic signaling pathways or recruit the immune system to destroy the tumor (Labrijn et al., Nature Reviews Drug Discovery, 2019). However, the effectiveness of targeting these molecules is often limited by 'on-target, off-tumor' toxicities if the target is also present on vital normal tissues, as well as the potential for tumors to downregulate target expression to escape treatment (Scott et al., 2012).

Other names

Tumor-associated antigens (TAAs)Tumor-specific antigens (TSAs)Cancer cell surface markersNeoantigensSurfaceome

Binding to extracellular domains to inhibit oncogenic signaling, induce antibody-dependent cellular cytotoxicity (ADCC), or deliver cytotoxic payloads directly to malignant cells.