2. Academic Validation
  3. NHWD-870 suppresses tumor proliferation via the BRD4/STRADA/CCND1 axis in small cell lung cancer

NHWD-870 suppresses tumor proliferation via the BRD4/STRADA/CCND1 axis in small cell lung cancer

  • Lung Cancer. 2025 Dec:210:108841. doi: 10.1016/j.lungcan.2025.108841.
Linrui Ma 1,  Xiangyu Zhang 2,  Shidong Xu 1,  Jiacheng Dai 1,  Zhe Huang 1,  Zhaohui Ruan 1,  Yuda Zhang 1,  Xuexue Zhou 1,  Yuanze Sun 1,  Yahui Chen 1,  Huan Yan 1,  Chun Zou 1,  Si Qi Xiang 1,  Jingyi Li 1,  Yangqian Chen 1,  Tian Xu 1,  Renzhi Zhang 1,  Dan Yang 1,  Fang Tian 1,  Nachuan Zou 1,  Yi Liao 1,  Jie Zou 1,  Wenjuan Jiang 1,  Xue Chen 1,  Jin Zhang 1,  Jun Deng 1,  Hua Xiang 1,  Liang Zeng 3,  Yongchang Zhang 4
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
  • 2 Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • 3 Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China. Electronic address: [email protected].
  • 4 Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Department of Medical Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: [email protected].
PMID: 41242286 DOI: 10.1016/j.lungcan.2025.108841
Abstract

Background: Small cell lung Cancer (SCLC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. The lack of effective targeted therapies for SCLC is a major limitation of this field. Bromodomain and Extra-Terminal (BET) inhibitors have emerged as a promising class of Anticancer agents. This study aimed to evaluate the preclinical efficacy and mechanism of action of NHWD-870, a novel BET inhibitor targeting BRD4, in SCLC.

Method: The therapeutic effects of NHWD-870 on SCLC have been validated through compassionate use. The anti-tumor effects of NHWD-870 were explored using in vitro and in vivo models. CCK-8 assays and flow cytometry were utilized to examine cell viability, Apoptosis, and mechanisms of cell cycle arrest. The in vivo effectiveness of NHWD-870 was evaluated using cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of SCLC. Mechanistic studies involving RNA Sequencing, Western blotting, qPCR, and transfection were conducted to investigate and confirm the underlying mechanisms of NHWD-870.

Result: Our study observed the efficacy of NHWD-870 in a patient with SCLC. NHWD-870 demonstrated robust anti-tumor activity against SCLC in both in vitro and in vivo models, effectively halting tumor growth, inducing Apoptosis, and disrupting the cell cycle. RNA Sequencing confirmed that the cell cycle is its primary pathway of action, with BRD4, STRADA, and CCND1 identified as key targets.

Conclusion: NHWD-870 exhibits anti-tumor activity both in vitro and in vivo against SCLC, primarily by regulating the BRD4/STRADA/CCND1 axis and inhibiting the transition of the cell cycle from the G1 phase to the S phase. These findings highlight the therapeutic potential of NHWD-870 as a novel BET inhibitor for SCLC treatment and provide a molecular basis for further clinical development.

Keywords

BRD4; Cell cycle; NHWD-870; Small cell lung cancer.

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