Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 136-144 http://medscipublisher.com/index.php/cge 139 Figure 1 Combination Therapies with CAR-T Cells (Adopted from Zhou et al., 2024) Image caption: ①: Combining CAR-T cells with BTK inhibitors inhibits BTK in the B-cell signaling pathway, reducing malignant B-cell proliferation; ②: Combining CAR-T cells with PI3K inhibitors interferes with tumor cell growth and survival by inhibiting the PI3K signaling pathway; ③: Combining CAR-T cells with BCL-2 inhibitors promotes tumor cell apoptosis by inhibiting the BCL-2 protein; ④: Combining CAR-T cells with GSI prevents the shedding of BCMA from the surface of tumor cells by inhibiting γ-secretase; ⑤: Combining CAR-T cells with Lenalidomide recruits the E3 ubiquitin ligase CRL4CRBN, inducing the degradation of IKZF1 and IKZF3; ⑥: Combining CAR-T cells with PD-1/PD-L1 inhibitors blocks the PD-1/PD-L1 signaling pathway to counteract the tumor cells’ immune evasion mechanism; ⑦: Combining CAR-T cells with Radiotherapy directly kills tumor cells, enhancing the effectiveness of CAR-T therapy; ⑧: Combining CAR-T cells with Hematopoietic Stem Cell Transplantation rebuilds the patient’s immune system to support the sustained anti-tumor activity of CAR-T cells (Adopted from Zhou et al., 2024) The disease changes were monitored through methods such as imaging examinations, minimal residual disease (MRD) detection, and regular laboratory tests to detect signs of recurrence as early as possible (Xiang et al., 2020). Actual clinical studies have shown that the therapeutic effect is similar to the results in key trials, which also proves that these evaluation indicators and monitoring methods are reliable (Chen, 2024; Goyco Vera et al., 2024). 4.2 Toxicity: cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome CAR-T cell therapy has some serious potential side effects, the most prominent of which are cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome (ICANS) (Gomez et al., 2021). Up to 80% of patients will develop CRS, with symptoms manifested as fever, low blood pressure and multiple organ dysfunction. This is because when CAR-T cells are activated, they release a large amount of cytokines (Zheng et al., 2025). According to statistics, 10-37% of patients will develop ICANS, with symptoms ranging from mental confusion, body tremors to epileptic seizures, cerebral edema and other neurological problems (Hutton et al., 2019; Roex et al., 2020; Xiang et al., 2020; Chohan et al., 2023). The occurrence probability and severity of these side effects vary depending on the type of disease, the patient's own condition, and the design of CAR-T cells. Especially in patients who have undergone multiple prior treatments, they are more likely to occur (Roex et al., 2020; Xiang et al., 2020; Chohan et al., 2023). In addition, long-term adverse reactions such as cytopenia and increased risk of infection also require continuous attention (Gomez et al., 2021; Zheng et al., 2025).
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