Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death

Cu, a common essential trace element in the human body, is involved in multiple physiological and pathological processes. Cuproptosis, a recently proposed form of cell death, is triggered by Cu overload. It primarily targets lipoylated proteins in the tricarboxylic acid cycle, induces proteotoxic stress, and impairs mitochondrial respiration. Cuproptosis can induce immunogenic cell death (ICD), which triggers adaptive immunity in response to cellular stress, thereby stimulating an immune response. Conversely, ICD may also induce cuproptosis, indicating an interaction between the two; this mechanism should provide insights in lung cancer treatment. Lung cancer is a common disease that endangers human health and is characterized by high mortality and incidence rates. Despite the availability of therapeutic regimens such as surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors, their prognosis remains controversial. This review innovatively proposes that the combination of these two forms of cell death, together with their interaction, may target biomarkers of various lung cancers. This study provides a theoretical basis for addressing the challenges encountered in lung cancer treatment.