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The JAK1 Inhibitor Golidocitinib Boosts Therapeutic Potency of DLL3-Targeted CAR-T Therapy for Small Cell Lung Cancer

delete2026-07-20
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M
Mengwei Li
Y
Yao Zhang
F
Fangqi Li
Y
Yuchen Xia
W
Wanting Wang
J
Jingwen Li
H
Huawei Du
R
Ruiting Tan
H
Huiping Qiang
Y
Yue Wang
S
Shuhui Cao
L
Litang Huang
E
Erpeng Wu
Y
Yu Yang
B
Bo Zhang
X
Xuanming Yang
Y
Yan Zhou *
C
Cheng Zhang *
钟华 (Hua Zhong) *
DOI:10.1016/j.phrs.2026.108347delete
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Abstract

Abstract

En 中文
Small cell lung cancer (SCLC) is an aggressive malignancy with limited effective therapeutic options. DLL3-targeted CAR-T therapy shows promising anti-tumor potential but is often restricted by T-cell exhaustion, which impairs its long-term efficacy. In the present study, we found that golidocitinib, a highly selective JAK1 inhibitor, induces apoptosis in SCLC cells in vitro via inhibiting STAT3 phosphorylation and regulating apoptosis‑associated genes. It also reduced the expression of exhaustion markers in anti-DLL3 CAR-T cells, promoted the formation of memory T cell phenotypes, and enhanced CAR-T cell persistence both in vitro and in vivo. When combined with anti-DLL3 CAR-T therapy, golidocitinib significantly augmented anti-tumor efficacy in both in vitro cytotoxicity assays and in vivo models, without obvious organ toxicity. These findings collectively demonstrate the dual anti-tumor effects of golidocitinib, thus providing a novel and promising strategy for SCLC treatment.
Keywords:
SCLC
JAK1
golidocitinib
DLL3
CAR-T
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Journal

Pharmacological Research cover
Pharmacological Research
IF:
10.5
Papers:
8.7K
Citations:
3.6W

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S
shanghai jiao tong university
Scholars:
15.1W
Papers: 11.5W
Citations: 159
N
Northern Jiangsu People's Hospital
Scholars:
69
Papers: 33
Citations: 942
S
shanghai jiao tong university school of medicine
Scholars:
1.1K
Papers: 278
Citations: 0
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