高水平论文推送8——肿瘤学

各单位、部门，全体科研人员：

为促进学术交流与知识共享，助力科研人员及时了解各领域前沿动态与最新研究成果，现决定定期推送我校学者发表的高水平论文。每篇推送将包含论文题目、作者信息、发表期刊/会议、核心观点摘要、研究亮点及创新点等关键内容。

本期主题为肿瘤学，希望为相关研究者的学术研究提供有益参考，提升学术水平。请有关单位、部门加强学校高水平论文的推介工作。

科学技术部

2025年9月28日

1、Signaling pathways in rheumatoid arthritis: implications for targeted therapy

类风湿性关节炎中的信号通路：对靶向治疗的启示

Issue SIGNAL TRANSDUCTION AND TARGETED THERAPY 2023, Volume 8 Issue 1

期刊：《信号传导及靶向治疗》2023年，第8卷 第1期

Author Ding Qian / Hu Wei / Wang Ran / Yang Qinyan / Zhu Menglin / Li Meng / Cai Jianghong / Rose Peter / Mao Jianchun / Zhu Yi Zhun

Abstract Rheumatoid arthritis (RA) is an incurable systemic autoimmune disease. Disease progression leads to joint deformity and associated loss of function, which significantly impacts the quality of life for sufferers and adds to losses in the labor force. In the past few decades, RA has attracted increased attention from researchers, the abnormal signaling pathways in RA are a very important research field in the diagnosis and treatment of RA, which provides important evidence for understanding this complex disease and developing novel RA-linked intervention targets. The current review intends to provide a comprehensive overview of RA, including a general introduction to the disease, historical events, epidemiology, risk factors, and pathological process, highlight the primary research progress of the disease and various signaling pathways and molecular mechanisms, including genetic factors, epigenetic factors, summarize the most recent developments in identifying novel signaling pathways in RA and new inhibitors for treating RA. therapeutic interventions including approved drugs, clinical drugs, pre-clinical drugs, and cutting-edge therapeutic technologies. These developments will hopefully drive progress in new strategically targeted therapies and hope to provide novel ideas for RA treatment options in the future.

Citation Format [1]Ding Qian, Hu Wei, Wang Ran, et al.Signaling pathways in rheumatoid arthritis: implications for targeted therapy[J].SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(1).

2、Nanomedicine in cancer therapy

纳米药物在癌症治疗中的应用

Issue SIGNAL TRANSDUCTION AND TARGETED THERAPY 2023, Volume 8 Issue 1

期刊：《信号传导及靶向治疗》2023年，第8卷 第1期

Author Fan Dahua / Cao Yongkai / Cao Meiqun / Wang Yajun / Cao Yongliang / Gong Tao

Abstract Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances in nanotechnology, accompanied by our growing understanding of cancer biology and nano-bio interactions, have led to the development of a series of nanocarriers, which aim to improve the therapeutic efficacy while reducing off-target toxicity of the encapsulated anticancer agents through tumor tissue-, cell-, or organelle-specific targeting. However, the vast majority of nanocarriers do not possess hierarchical targeting capability, and their therapeutic indices are often compromised by either poor tumor accumulation, inefficient cellular internalization, or inaccurate subcellular localization. This Review outlines current and prospective strategies in the design of tumor tissue-, cell-, and organelle-targeted cancer nanomedicines, and highlights the latest progress in hierarchical targeting technologies that can dynamically integrate these three different stages of static tumor targeting to maximize therapeutic outcomes. Finally, we briefly discuss the current challenges and future opportunities for the clinical translation of cancer nanomedicines.

Citation Format [1]Fan Dahua, Cao Yongkai, Cao Meiqun, et al.Nanomedicine in cancer therapy[J].SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(1).

3、A review of the clinical efficacy of FDA-approved antibody-drug conjugates in human cancers

FDA 批准的抗体药物偶联物在人类癌症中的临床疗效综述

Issue MOLECULAR CANCER 2024, Volume 23 Issue 1

期刊：《分子癌症》 2024 年，第 23 卷 第 1 期

Author Liu Kaifeng / Li Meijia / Li Yudong / Li Yutong / Chen Zixin / Tang Yiqi / Yang Meitian / Deng Guoquan / Liu Hongwei

Keywords Antibody-drug conjugates / Cancer therapy / Targeted drugs / FDA-approved / Clinical efficacy

Abstract While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody-drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)-approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

Citation Format [1]Liu Kaifeng, Li Meijia, Li Yudong, et al.A review of the clinical efficacy of FDA-approved antibody-drug conjugates in human cancers[J].MOLECULAR CANCER,2024,23(1).

4、DeepST: identifying spatial domains in spatial transcriptomics by deep learning

DeepST：通过深度学习识别空间转录组学中的空间域

Issue NUCLEIC ACIDS RESEARCH 2022, Volume 50 Issue 22

期刊：《核酸研究》 2022 年，第 50 卷 第 22 期

Author Xu Chang / Jin Xiyun / Wei Songren / Wang Pingping / Luo Meng / Xu Zhaochun / Yang Wenyi / Cai Yideng / Xiao Lixing / Lin Xiaoyu / Liu Hongxin / Cheng Rui / Pang Fenglan / Chen Rui / Su Xi / Hu Ying / Wang Guohua / Jiang Qinghua

Abstract Recent advances in spatial transcriptomics (ST) have brought unprecedented opportunities to understand tissue organization and function in spatial context. However, it is still challenging to precisely dissect spatial domains with similar gene expression and histology in situ. Here, we present DeepST, an accurate and universal deep learning framework to identify spatial domains, which performs better than the existing state-of-the-art methods on benchmarking datasets of the human dorsolateral prefrontal cortex. Further testing on a breast cancer ST dataset, we showed that DeepST can dissect spatial domains in cancer tissue at a finer scale. Moreover, DeepST can achieve not only effective batch integration of ST data generated from multiple batches or different technologies, but also expandable capabilities for processing other spatial omics data. Together, our results demonstrate that DeepST has the exceptional capacity for identifying spatial domains, making it a desirable tool to gain novel insights from ST studies.

Citation Format [1]Xu Chang, Jin Xiyun, Wei Songren, et al.DeepST: identifying spatial domains in spatial transcriptomics by deep learning[J].NUCLEIC ACIDS RESEARCH,2022,50(22).

5、mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

mTOR 信号通路及其抑制剂在癌症治疗中的进展与挑战

Issue CELL AND BIOSCIENCE 2020, Volume 10 Issue 1

期刊：《细胞与生物科学》 2020 年，第 10 卷 第 1 期

Author Zou Zhilin / Tao Tao / Li Hongmei / Zhu Xiao

Keywords mTOR signaling pathway / mTOR inhibitor / Tumor metabolism / Autophagy / Apoptosis

Abstract Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism. Therefore, the mTOR signaling pathway is a hot target in anti-tumor therapy research. In recent years, a variety of newly discovered mTOR inhibitors have entered clinical studies, and a variety of drugs have been proven to have high activity in combination with mTOR inhibitors. The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field.

Citation Format [1]Zou Zhilin, Tao Tao, Li Hongmei, et al.mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges[J].CELL AND BIOSCIENCE,2020,10(1).

6、Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial

特瑞普利单抗或安慰剂联合化疗作为晚期鼻咽癌的一线治疗：一项多中心随机 3 期试验

Issue NATURE MEDICINE 2021, Volume 27 Issue 9

期刊：《自然·医学》 2021 年，第 27 卷 第 9 期

Author Mai Hai-Qiang / Chen Qiu-Yan / Chen Dongping / Hu Chaosu / Yang Kunyu / Wen Jiyu / Li Jingao / Shi Ying-Rui / Jin Feng / Xu Ruilian / Pan Jianji / Qu Shenhong / Li Ping / Hu Chunhong / Liu Yi-Chun / Jiang Yi / He Xia / Wang Hung-Ming / Lim Wan-Teck / Liao Wangjun / He Xiaohui / Chen Xiaozhong / Liu Zhigang / Yuan Xianglin / Li Qi / Lin Xiaoyan / Jing Shanghua / Chen Yanju / Lu Yin / Hsieh Ching-Yun / Yang Muh-Hwa / Yen Chia-Jui / Samol Jens / Feng Hui / Yao Sheng / Keegan Patricia / Xu Rui-Hua

Abstract Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36-0.74), P = 0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18 February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364-0.997)). The incidence of grade >= 3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade >= 3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile. Interim analysis from the randomized phase 3 JUPITER-02 trial shows that the addition of anti-PD-1 toripalimab to standard gemcitabine/cisplatin as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma has manageable toxicity and improves progression-free survival, suggesting a potential new treatment standard in this setting.

Citation Format [1]Mai Hai-Qiang, Chen Qiu-Yan, Chen Dongping, et al.Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial[J].NATURE MEDICINE,2021,27(9).

7、The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

Wnt 信号在干细胞增殖与分化、人类疾病发生发展中的角色演变及治疗机遇

Issue GENES & DISEASES 2024, Volume 11 Issue 3

期刊：《基因与疾病》 2024 年，第 11 卷第 3 期

Author Yu Michael / Qin Kevin / Fan Jiaming / Zhao Guozhi / Zhao Piao / Zeng Wei / Chen Connie / Wang Annie / Wang Yonghui / Zhong Jiamin / Zhu Yi / Wagstaff William / Haydon Rex C. / Luu Hue H. / Ho Sherwin / Lee Michael J. / Strelzow Jason / Reid Russell R. / He Tong-Chuan

Keywords 13-Catenin / Cancer / Canonical Wnt / Disease / Non-canonical Wnt / Stem cells / Targeted therapy / Wnt signaling

Abstract The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (13-catenin dependent) and non-canonical (13-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differ-entiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues. This includes but is not limited to embryonic, hematopoietic, mesenchymal, gut, neural, and epidermal stem cells. Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties. Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders. Not surprisingly, aberrant Wnt signaling is also associated with a wide variety of diseases, including cancer. Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation, epithelialemesenchymal transition, and metastasis. Altogether, advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway. Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt, this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells, aberrations to the Wnt pathway associated with diseases, and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies. (c) 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Citation Format [1]Yu Michael, Qin Kevin, Fan Jiaming, et al.The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities[J].GENES & DISEASES,2024,11(3).

8、Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

典型与非典型Wnt信号通路:多层级介质、信号机制及主要通路交叉对话

Issue GENES & DISEASES 2024, Volume 11 Issue 1 103-134

期刊：（基因与疾病》 2024年，第11卷第一期

Author Qin Kevin / Yu Michael / Fan Jiaming / Wang Hongwei / Zhao Piao / Zhao Guozhi / Zeng Wei / Chen Connie / Wang Yonghui / Wang Annie / Schwartz Zander / Hong Jeffrey / Song Lily / Wagstaff William / Haydon Rex C. / Luu Hue H. / Ho Sherwin H. / Strelzow Jason / Reid Russell R. / He Tong-Chuan / Shi Lewis L.

Keywords beta-catenin / Canonical Wnt / Noncanonical Wnt / Signal transduction / Signaling crosstalk

Abstract Wnt signaling plays a major role in regulating cell proliferation and differentiation. The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either through beta-catenin in the canonical pathway or through a series of other proteins in the noncanonical pathway. Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body, establishing the complex interplay between Wnt signaling and other signaling pathways. This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes. Dysregulation of this system has been implicated in many diseases affecting a wide array of organ systems, including cancer and embryological defects, and can even cause embryonic lethality. The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments. However, both stimulatory and inhibitory treatments come with potential risks that need to be addressed. This review synthesized much of the current knowledge on the Wnt signaling pathway, beginning with the history of Wnt signaling. It thoroughly described the different variants of Wnt signaling, including canonical, noncanonical Wnt/PCP, and the noncanonical Wnt/Ca2+ pathway. Further description involved each of its components and their involvement in other cellular processes. Finally, this review explained the various other pathways and processes that crosstalk with Wnt signaling. (c) 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons. org/licenses/by-nc-nd/4.0/).

Citation Format [1]Qin Kevin, Yu Michael, Fan Jiaming, et al.Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk[J].GENES & DISEASES,2024,11(1):103-134.

9、Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial

贝莫苏拜单抗联合安罗替尼及化疗治疗广泛期小细胞肺癌:一项随机川期研究

Issue NATURE MEDICINE 2024, Volume 30 Issue 10

期刊：《自然-医学》2024年第30卷第10期

Author Cheng Ying / Chen Jianhua / Zhang Wei / Xie Chao / Hu Qun / Zhou Ningning / Huang Chun / Wei Shihong / Sun Hong / Li Xingya / Yu Yan / Lai Jinhuo / Yang Huaping / Fang Haohui / Chen Hualin / Zhang Peng / Gu Kangsheng / Wang Qiming / Shi Jianhua / Yi Tienan / Xu Xingxiang / Ye Xianwei / Wang Daqing / Xie Conghua / Liu Chunling / Zheng Yulong / Lin Daren / Zhuang Wu / Lu Ping / Yu Guohua / Li Jinzhang / Gu Yuhai / Li Baolan / Wu Rong / Jiang Ou / Wang Zaiyi / Wu Guowu / Lin Haifeng / Zhong Diansheng / Xu Yanhua / Shu Yongqian / Wu Di / Chen Xingwu / Wang Jie / Wang Minghui / Yang Runxiang

Abstract Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607. In this triple-arm, placebo-controlled phase 3 trial, first-line treatment of patients with extensive-stage small-cell lung cancer with the anti-PD-L1 benmelstobart, tyrosine kinase inhibitor anlotinib and chemotherapy (CT) showed improved survival outcomes compared with anlotinib and CT or CT alone.

Citation Format [1]Cheng Ying, Chen Jianhua, Zhang Wei, et al.Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial[J].NATURE MEDICINE,2024,30(10).