Tumor cell surface proteome (Surfaceome)

The tumor cell plasma membrane and its associated surface proteins, collectively known as the surfaceome, represent the critical interface between the neoplastic cell and its external environment [Bausch-Fluck et al., 2018, PNAS]. This compartment is enriched with a diverse array of proteins, including signaling receptors, transporters, and adhesion molecules, which are often dysregulated to promote oncogenic signaling, nutrient uptake, and immune system evasion [Alix-Panabières & Pantel, 2017, Chemical Reviews]. Due to their extracellular accessibility, these proteins are the primary targets for modern oncology therapeutics such as monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies [Scott et al., 2012, Nature Reviews Cancer]. While targeting these proteins allows for high specificity in some cases, the primary challenge remains the on-target, off-tumor effect, where the target is also expressed at lower levels on vital healthy tissues [Sliwkowski & Mellman, 2013, Science]. Understanding the spatial and temporal dynamics of the tumor surfaceome is essential for developing next-generation precision medicines that can overcome tumor heterogeneity and resistance mechanisms [Haura et al., 2011, Nature Reviews Clinical Oncology].

Other names

Tumor cell plasma membrane and associated surface proteinsCancer cell surfaceomeTumor-associated surface antigensCell surface proteome

Therapeutic agents targeting surface proteins employ diverse mechanisms, including the blockade of growth factor signaling, induction of antibody-dependent cellular cytotoxicity (ADCC), targeted delivery of cytotoxins via antibody-drug conjugates (ADCs), and the disruption of immune checkpoints to restore anti-tumor immunity [Scott et al., 2012, Nature Reviews Cancer; Sliwkowski & Mellman, 2013, Science].