Tumor-associated cell surface biomarkers and receptors (TAA/TSA)

Tumor-associated cell surface biomarkers and receptors are a broad class of molecules expressed on the exterior of cancer cells that facilitate tumor growth, immune evasion, and metabolic adaptation [1]. These targets include receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and various cluster of differentiation (CD) antigens that are either overexpressed, mutated, or neo-expressed in malignant tissues compared to normal cells [2]. In clinical oncology, these surface proteins are leveraged for both diagnostic imaging and targeted therapy, serving as the docking sites for monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and T-cell engagers [3]. For instance, receptors like EGFR and HER2 are pivotal in driving proliferative signaling, while immune checkpoints like PD-L1 modulate the tumor microenvironment to suppress anti-tumor immunity [4]. The therapeutic utility of these targets is often limited by their expression profile in healthy tissues, leading to potential "on-target, off-tumor" toxicities [5]. Furthermore, the propensity of tumors to develop resistance through target downregulation or "antigen escape" remains a significant challenge in maintaining long-term treatment efficacy [6]. Consequently, the identification of highly specific tumor-specific antigens (TSAs) remains a cornerstone of precision medicine and next-generation immunotherapy development. References: [1] NIH National Cancer Institute, Tumor Marker; [2] Scott et al. (2012) Nature Reviews Cancer; [3] Hafeez et al. (2020) Molecules; [4] Pardoll (2012) Nature Reviews Cancer; [5] Majzner & Mackall (2018) Cancer Discovery; [6] Vigneron (2015) BioMed Research International.

Other names

Tumor-associated antigensTumor-specific antigensCancer cell surface markersOnco-antigensTumor surface receptors

Drugs targeting these molecules typically function through competitive inhibition of ligand binding, induction of antibody-dependent cellular cytotoxicity (ADCC), delivery of cytotoxic payloads via internalizing receptors, or redirection of T-cell activity toward the tumor cell [2, 3].