Cancer stem cell surface antigens enriched on ALDHhigh CSCs (CSC-ALDH-Ag)

Cancer stem cell (CSC) surface antigens enriched on ALDHhigh cells represent a diverse group of proteins expressed on a subpopulation of tumor cells characterized by high aldehyde dehydrogenase (ALDH) activity (Ginestier et al., 2007). ALDH is an intracellular enzyme responsible for the oxidation of aldehydes and serves as a functional marker for stemness, contributing to drug resistance by metabolizing certain chemotherapeutic agents (Li et al., 2017). The surface antigens associated with these ALDHhigh cells, such as CD44, CD133, and EpCAM, play critical roles in mediating interactions with the tumor microenvironment and activating signaling pathways like Wnt and Notch that sustain the CSC phenotype (Medema, 2013; Takebe et al., 2015). Because ALDHhigh CSCs are often resistant to standard radiation and chemotherapy, they are considered primary drivers of tumor relapse and metastasis (Zhao et al., 2018). Therapeutic strategies targeting these surface antigens or the ALDH enzyme itself, such as the use of disulfiram or specific monoclonal antibodies, are being developed to specifically eliminate this resilient cell population (Liu et al., 2012; Gomez-Roca et al., 2015). Targeting these markers aims to deplete the tumor-initiating cell reservoir and improve long-term patient outcomes. However, the high degree of plasticity between CSC and non-CSC states remains a significant challenge for these therapies.

Other names

ALDH+ CSC markersALDH-high cancer stem cell surface proteinsCSC-associated antigensAldehyde dehydrogenase-high cancer stem cell markers

Targeting these antigens or the associated ALDH activity aims to deplete the cancer stem cell pool, inhibit self-renewal pathways (such as Wnt/Notch), and sensitize tumors to conventional chemotherapy by removing cells capable of aldehyde-mediated detoxification (Li et al., 2017; Liu et al., 2012).