Fucosyl-GM1 glycosphingolipid antigen (Fuc-GM1)

Fucosyl-GM1 (Fuc-GM1) is a monosialoganglioside and tumor-associated carbohydrate antigen (TACA) that is highly overexpressed in approximately 60% to 90% of small cell lung cancer (SCLC) cases [1, 3]. While it is present during fetal development and in restricted adult tissues such as peripheral sensory neurons and dorsal root ganglia, its expression is virtually absent in most healthy adult organs, making it an attractive target for immunotherapy [3, 7]. Biologically, Fuc-GM1 is involved in modulating axonal outgrowth and has been implicated in promoting tumor cell proliferation, angiogenesis, and immune evasion [3, 7, 16]. Therapeutic strategies targeting Fuc-GM1 include monoclonal antibodies like atigotatug (BMS-986012), which induce tumor cell death through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP) [1, 2, 4]. Clinical trials are currently evaluating these agents as monotherapy or in combination with checkpoint inhibitors and chemotherapy for the treatment of extensive-stage SCLC [5, 12]. The restricted expression profile of Fuc-GM1 helps minimize off-target effects, although pruritus and potential neurotoxicity remain considerations for drug development [3, 14]. Recent research also explores Fuc-GM1 as a target for antibody-drug conjugates and T-cell engaging bispecific antibodies [13, 16]. Overall, Fuc-GM1 represents a highly specific biomarker and therapeutic target for aggressive neuroendocrine tumors with significant unmet medical needs [1, 17].

Other names

FucGM1Fuc-GM1Fucosyl-monosialoganglioside-1α1,2-fucosyl-GM1Fucosyl-GM1 ganglioside

Induction of tumor cell death via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP) [1, 2, 4].