ATP-binding cassette sub-family B member 5 (ABCB5) (ABCB5)

ATP-binding cassette sub-family B member 5 (ABCB5) is a transmembrane protein belonging to the P-glycoprotein family of ATP-binding cassette (ABC) transporters [4, 7]. It is predominantly recognized as a marker for cancer stem cells, particularly in malignant melanoma, where it plays a critical role in tumor initiation, progression, and metastasis [1, 4]. ABCB5 functions as an energy-dependent efflux pump that exports a wide range of chemotherapeutic agents, including doxorubicin and 5-fluorouracil, thereby conferring multidrug resistance to aggressive tumor subpopulations [4, 9]. Beyond its transport activity, ABCB5 regulates the maintenance of the cancer stem cell phenotype through the modulation of pro-inflammatory cytokine signaling circuits, such as the IL-1beta/IL-8/CXCR1 pathway [4]. In normal human physiology, ABCB5 is expressed in limbal stem cells of the eye and dermal mesenchymal stem cells, where it is essential for corneal repair and tissue homeostasis [7, 13]. Therapeutic targeting of ABCB5, often via monoclonal antibodies, aims to sensitize resistant tumors to chemotherapy and deplete the tumor-initiating cell pool [1, 4, 5]. However, the expression of ABCB5 in healthy progenitor populations presents a significant challenge for drug safety and requires precise targeting to avoid off-target toxicities [10, 13].

Other names

ABCB5alphaABCB5betaP-glycoprotein ABCB5ABCB5 P-gp

ABCB5 acts as an energy-dependent efflux transporter that reduces the intracellular accumulation of various chemotherapeutic drugs [4, 7]. Drugs targeting ABCB5, such as monoclonal antibodies, work by inhibiting this efflux function and disrupting the IL-1beta/IL-8/CXCR1 cytokine signaling circuit to sensitize tumors and deplete cancer stem cell populations [1, 4, 5].