¸ßˮƽÂÛÎÄÍÆËÍ4¡ª¡ªÖ×Áöѧ

¸÷µ¥Î»¡¢²¿ÃÅ£¬È«Ìå¿ÆÑÐÈËÔ±£º

Ϊ´Ù½øѧÊõ½»Á÷Óë֪ʶ¹²Ïí£¬ÖúÁ¦¿ÆÑÐÈËÔ±¼°Ê±Á˽â¸÷ÁìÓòÇ°Ñض¯Ì¬Óë×îÐÂÑо¿³É¹û£¬ÏÖ¾ö¶¨¶¨ÆÚÍÆËÍ°ÄÃŽðɳ³ÇÖÐÐÄ_°ÄÃÅÊ®´óµç×ÓÓÎÏ·appÏÂÔØ-¡¾Ê×Ò³¡¿@ѧÕß·¢±íµÄ¸ßˮƽÂÛÎÄ¡£Ã¿ÆªÍÆËͽ«°üº¬ÂÛÎÄÌâÄ¿¡¢×÷ÕßÐÅÏ¢¡¢·¢±íÆÚ¿¯/»áÒé¡¢ºËÐĹ۵ãÕªÒª¡¢Ñо¿ÁÁµã¼°´´ÐµãµÈ¹Ø¼üÄÚÈÝ¡£

±¾ÆÚÖ÷ÌâΪÖ×Áöѧ£¬Ï£ÍûΪÏà¹ØÑо¿ÕßµÄѧÊõÑо¿ÌṩÓÐÒæ²Î¿¼£¬ÌáÉýѧÊõˮƽ¡£ÇëÓйص¥Î»¡¢²¿ÃżÓǿѧУ¸ßˮƽÂÛÎĵÄÍƽ鹤×÷¡£

¿Æѧ¼¼Êõ²¿

2025Äê8ÔÂ20ÈÕ

Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12)

ÐŵÏÀûµ¥¿¹ÁªºÏ²¬ÀàÓ뼪Î÷Ëû±õ×÷ΪÍíÆÚ»òתÒÆÐÔÁÛ×´·ÇСϸ°û·Î°©Ò»ÏßÖÎÁÆ·½°¸£ºÒ»ÏîËæ»ú¡¢Ë«Ã¤¢óÆÚÁÙ´²ÊÔÑ飨ORIENT-12£©½á¹û

Issue JOURNAL OF THORACIC ONCOLOGY 2021, Volume 16 Issue 9 1501-1511

ÆÚ¿¯£º¡¶Ðز¿Ö×ÁöÔÓÖ¾¡·£¨JOURNAL OF THORACIC ONCOLOGY£©£¬2021Ä꣬µÚ16¾íµÚ9ÆÚ£¬1501-1511Ò³

Author Zhou Caicun / Wu Lin / Fan Yun / Wang Zhehai / Liu Lianke / Chen Gongyan / Zhang Li / Huang Dingzhi / Cang Shundong / Yang Zhixiong / Zhou Jianying / Zhou Chengzhi / Li Baolan / Li Juan / Fan Min / Cui Jiuwei / Li Yuping / Zhao Hui / Fang Jian / Xue Jianxin / Hu Chengping / Sun Ping / Du Yingying / Zhou Hui / Wang Shuyan / Zhang Wen

Keywords Sintilimab / Squamous NSCLC / Platinum and gemcitabine / Combination / First-line

Abstract

Introduction: The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti-programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP. Methods: ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People's Republic of China (ClinicalTrials.gov, number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee. Results: Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422-0.681], p < 0.00001). Treatment-emergent adverse events of grade 3 or worse occurred in 86.6% patients in the sintilimab-GP group and in 83.1% in the placebo-GP group. The incidence of treatment-emergent adverse event leading to death was 4.5% and 6.7% in the two treatment groups, respectively. Conclusions: Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Cite this article as: [1]Zhou Caicun, Wu Lin, Fan Yun, et al.Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12)[J].JOURNAL OF THORACIC ONCOLOGY,2021,16(9):1501-1511.

Nanoparticles advanced from preclinical studies to clinical trials for lung cancer therapy

ÄÉÃ׿ÅÁ£´ÓÁÙ´²Ç°Ñо¿µ½ÁÙ´²ÊÔÑéÔڷΰ©ÖÎÁÆÖеÄÓ¦ÓýøÕ¹

Issue CANCER NANOTECHNOLOGY 2023, Volume 14 Issue 1

ÆÚ¿¯£º¡¶°©Ö¢ÄÉÃ×¼¼Êõ¡·£¨CANCER NANOTECHNOLOGY£©£¬2023Ä꣬µÚ14¾íµÚ1ÆÚ

Author Liu Yifan / Cheng Wenxu / Xin HongYi / Liu Ran / Wang Qinqi / Cai Wenqi / Peng Xiaochun / Yang Fuyuan / Xin HongWu

Keywords Lung cancer / Nanoparticle / Immune targeted therapy / Nanotherapy

Abstract

Lung cancer is the leading cause of cancer mortality. As a heterogeneous disease, it has different subtypes and various treatment modalities. In addition to conventional surgery, radiotherapy and chemotherapy, targeted therapy and immunotherapy have also been applied in the clinics. However, drug resistance and systemic toxicity still cannot be avoided. Based on the unique properties of nanoparticles, it provides a new idea for lung cancer therapy, especially for targeted immunotherapy. When nanoparticles are used as carriers of drugs with special physical properties, the nanodrug delivery system ensures the accuracy of targeting and the stability of drugs while increasing the permeability and the aggregation of drugs in tumor tissues, showing good anti-tumor effects. This review introduces the properties of various nanoparticles including polymer nanoparticles, liposome nanoparticles, quantum dots, dendrimers, and gold nanoparticles and their applications in tumor tissues. In addition, the specific application of nanoparticle-based drug delivery for lung cancer therapy in preclinical studies and clinical trials is discussed.

Cite this article as: [1]Liu Yifan, Cheng Wenxu, Xin HongYi, et al.Nanoparticles advanced from preclinical studies to clinical trials for lung cancer therapy[J].CANCER NANOTECHNOLOGY,2023,14(1).

The RNA m6A Reader YTHDF1 Is Required for Acute Myeloid Leukemia Progression

RNA N6-¼×»ùÏÙÜÕÔĶÁÆ÷YTHDF1¶Ô¼±ÐÔËèϵ°×Ѫ²¡½øÕ¹ÖÁ¹ØÖØÒª

Issue CANCER RESEARCH 2023, Volume 83 Issue 6 845-860

ÆÚ¿¯£º¡¶°©Ö¢Ñо¿¡·£¨CANCER RESEARCH£©£¬2023Ä꣬µÚ83¾íµÚ6ÆÚ£¬845-860Ò³

Author Hong Yun-Guang / Yang Zhigang / Chen Yan / Liu Tian / Zheng Yuyuan / Zhou Chun / Wu Guo-Cai / Chen Yinhui / Xia Juan / Wen Ruiting / Liu Wenxin / Zhao Yi / Chen Jin / Gao Xiangwei / Chen Zhanghui

Abstract

N-6-methyladenosine (m⁶A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myelogenous leukemia (AML). Identification of the key regulators of m⁶A modifications in AML could provide further insights into AML biology and uncover more effective therapeutic strategies for patients with AML. Here, we report overexpression of YTHDF1, an m⁶A reader protein, in human AML samples at the protein level with enrichment in leukemia stem cells (LSC). Where-as YTHDF1 was dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuated self-renewal, proliferation, and leukemic capacity of primary human and mouse AML cells in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of cyclin E2 in an m⁶A-dependent manner. Structure-based virtual screening of FDA-approved drugs identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocked the direct binding of YTHDF1 with m⁶A-modified mRNAs and inhibited YTHDF1-regulated cyclin E2 translation. Moreover, tegaserod reduced the viability of patient-derived AML cells in vitro and prolonged survival in patient-derived xenograft models. Together, our study defines YTHDF1 as an integral regulator of AML progression by regulating the expression of m⁶A-modified mRNAs, which might serve as a potential therapeutic target for AML. Significance: The m⁶A reader YTHDF1 is required for progres-sion of acute myelogenous leukemia and can be targeted with the FDA-approved drug tegaserod to suppress leukemia growth.

Cite this article as: [1]Hong Yun-Guang, Yang Zhigang, Chen Yan, et al.The RNA m<SUP>6</SUP>A Reader YTHDF1 Is Required for Acute Myeloid Leukemia Progression[J].CANCER RESEARCH,2023,83(6):845-860.

Microsatellite instability: a review of what the oncologist should know

΢ÎÀÐDz»Îȶ¨£ºÖ×Áö¿ÆÒ½ÉúÓ¦Á˽âµÄÏà¹Ø֪ʶ×ÛÊö

Issue CANCER CELL INTERNATIONAL 2020, Volume 20 Issue 1

ÆÚ¿¯£º¡¶°©Ö¢Ï¸°û¹ú¼Ê¡·£¨CANCER CELL INTERNATIONAL£©£¬2020Ä꣬µÚ20¾íµÚ1ÆÚ

Author Li Kai / Luo Haiqing / Huang Lianfang / Luo Hui / Zhu Xiao

Keywords MSI / Cancer / MSI-H / dMMR / Microsatellite DNA

Abstract

The patients with high microsatellite instability (MSI-H)/mismatch repair deficient (dMMR) tumors recently have been reported that can benefit from immunotherapy, and MSI can be used as a genetic instability of a tumor detection index. However, many studies have shown that there are many heterogeneous phenomena in patients with MSI tumors in terms of immunotherapy, prognosis and chemotherapy sensitivity. Here we mainly review the research results of MSI detection methods, the mechanisms of MSI occurrence and its relationship with related tumors, aiming to make a brief analysis of the current research status of MSI and provide comparable reference and guidance value for further research in this field.

Cite this article as: [1]Li Kai, Luo Haiqing, Huang Lianfang, et al.Microsatellite instability: a review of what the oncologist should know[J].CANCER CELL INTERNATIONAL,2020,20(1).

Toripalimab plus chemotherapy in treatment-naive, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial

ÌØÈðÆÕÀûµ¥¿¹ÁªºÏ»¯ÁÆÖÎÁƳõÖÎÍíÆÚʳ¹ÜÁÛ°©£¨JUPITER-06£©£ºÒ»Ïî¶àÖÐÐÄ¢óÆÚÁÙ´²ÊÔÑé

Issue CANCER CELL 2022, Volume 40 Issue 3 277

ÆÚ¿¯£º¡¶°©Ö¢Ï¸°û¡·£¨CANCER CELL£©£¬2022Ä꣬µÚ40¾íµÚ3ÆÚ£¬277Ò³

Author Wang Zi-Xian / Cui Chengxu / Yao Jun / Zhang Yanqiao / Li Mengxia / Feng Jifeng / Yang Shujun / Fan Yun / Shi Jianhua / Zhang Xizhi / Shen Lin / Shu Yongqian / Wang Cailian / Dai Tianyang / Mao Teng / Chen Long / Guo Zengqing / Liu Bo / Pan Hongming / Cang Shundong / Jiang Yi / Wang Junye / Ye Min / Chen Zhendong / Jiang Da / Lin Qin / Ren Wei / Wang Junsheng / Wu Lin / Xu Yong / Miao Zhanhui / Sun Meili / Xie Conghua / Liu Ying / Wang Qifeng / Zhao Lina / Li Qi / Huang Canhong / Jiang Ke / Yang Kunyu / Li Daojun / Liu Yunpeng / Zhu Zhitu / Chen Rixin / Jia Liqun / Li Wei / Liao Wangjun / Liu Hong-Xu / Ma Daiyuan / Ma Jie / Qin Yanru / Shi Zhihong / Wei Qichun / Xiao Ke / Zhang Yan / Zhang Ying / Chen Xin / Dai Guanghai / He Jianxing / Li Junhe / Li Guanghui / Liu Yong / Liu Zhihua / Yuan Xianglin / Zhang Junping / Fu Zhichao / He Yifu / Ju Fang / Liu Zheng / Tang Peng / Wang Tiejun / Wang Weibo / Zhang Jing / Luo Xianming / Tang Xiongwen / May Rena / Feng Hui / Yao Sheng / Keegan Patricia / Xu Rui-Hua / Wang Feng

Abstract

Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naive advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the pre specified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p < 0.0001). The pre specified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade R3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naive, advanced ESCC, with a manageable safety profile.

Cite this article as: [1]Wang Zi-Xian, Cui Chengxu, Yao Jun, et al.Toripalimab plus chemotherapy in treatment-naive, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial[J].CANCER CELL,2022,40(3):277.

RNA sequencing: new technologies and applications in cancer research

RNA²âÐò£º°©Ö¢Ñо¿ÖеÄм¼ÊõÓëÓ¦ÓÃ

Issue JOURNAL OF HEMATOLOGY & ONCOLOGY 2020, Volume 13 Issue 1

ÆÚ¿¯£º¡¶ÑªÒºÑ§ÓëÖ×ÁöѧÔÓÖ¾¡·£¨JOURNAL OF HEMATOLOGY & ONCOLOGY£©£¬2020Ä꣬µÚ13¾íµÚ1ÆÚ

Author Hong Mingye / Tao Shuang / Zhang Ling / Diao Li-Ting / Huang Xuanmei / Huang Shaohui / Xie Shu-Juan / Xiao Zhen-Dong / Zhang Hua

Keywords RNA sequencing / Application / Cancer

Abstract

Over the past few decades, RNA sequencing has significantly progressed, becoming a paramount approach for transcriptome profiling. The revolution from bulk RNA sequencing to single-molecular, single-cell and spatial transcriptome approaches has enabled increasingly accurate, individual cell resolution incorporated with spatial information. Cancer, a major malignant and heterogeneous lethal disease, remains an enormous challenge in medical research and clinical treatment. As a vital tool, RNA sequencing has been utilized in many aspects of cancer research and therapy, including biomarker discovery and characterization of cancer heterogeneity and evolution, drug resistance, cancer immune microenvironment and immunotherapy, cancer neoantigens and so on. In this review, the latest studies on RNA sequencing technology and their applications in cancer are summarized, and future challenges and opportunities for RNA sequencing technology in cancer applications are discussed.

Cite this article as: [1]Hong Mingye, Tao Shuang, Zhang Ling, et al.RNA sequencing: new technologies and applications in cancer research[J].JOURNAL OF HEMATOLOGY & ONCOLOGY,2020,13(1).

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial

¿¹PD-1/CTLA-4Ë«ÌØÒìÐÔ¿¹Ì忨¶ÈÄáÀûµ¥¿¹ÖÎÁÆÍíÆÚʵÌåÁöµÄ°²È«ÐÔÓ뿹Ö×Áö»îÐÔ£¨COMPASSION-03£©£ºÒ»Ïî¶àÖÐÐÄ¡¢¿ª·Å±êÇ©¢ñb/¢òÆÚÁÙ´²ÊÔÑé

Issue LANCET ONCOLOGY 2023, Volume 24 Issue 10 1134-1146

ÆÚ¿¯£º¡¶ÁøÒ¶µ¶?Ö×Áöѧ¡·£¨LANCET ONCOLOGY£©£¬2023Ä꣬µÚ24¾íµÚ10ÆÚ£¬1134-1146Ò³

Author Gao Xiangyu / Xu Nong / Li Ziyu / Shen Lin / Ji Ke / Zheng Zhong / Liu Dan / Lou Hanmei / Bai Li / Liu Tianshu / Li Yunxia / Li Yuzhi / Fan Qingxia / Feng Mei / Zhong Haijun / Huang Yi / Lou Ge / Wang Jing / Lin Xiaoyan / Chen Ye / An Ruifang / Li Changzheng / Zhou Qi / Huang Xin / Guo Zengqing / Wang Shubin / Li Guiling / Fei Junwei / Zhu Lijing / Zhu Hong / Li Xiumin / Li Fenghu / Liao Sihai / Min Qinghua / Tang Lei / Shan Fei / Gong Jifang / Gao Yunong / Zhou Jun / Lu Zhihao / Li Xiaofan / Li Jianjie / Ren Hui / Liu Xiaohong / Yang Hongxia / Li Wenting / Song Weifeng / Wang Zhongmin Maxwell / Li Baiyong / Xia Michelle / Wu Xiaohua / Ji Jiafu

Abstract

Background Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours.Methods This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. Findings Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14 center dot 6 months (IQR 13 center dot 1-17 center dot 5), the objective response rate was 32 center dot 3% (32 of 99; 95% CI 23 center dot 3-42 center dot 5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17 center dot 9 months (IQR 4 center dot 0-15 center dot 1), the objective response rate was 18 center dot 2% (four of 22; 95% CI 5 center dot 2-40 center dot 3). In the hepatocellular carcinoma cohort, with a median follow-up of 19 center dot 6 months (IQR 8 center dot 7-19 center dot 8), the objective response rate was 16 center dot 7% (four of 24; 95% CI 4 center dot 7-37 center dot 4). Interpretation Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours.Copyright (c) 2023 Elsevier Ltd. All rights reserved.

Cite this article as: [1]Gao Xiangyu, Xu Nong, Li Ziyu, et al.Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial[J].LANCET ONCOLOGY,2023,24(10):1134-1146.

Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11)

ÐŵÏÀûµ¥¿¹ÁªºÏÅàÃÀÇúÈûÓ벬Àà×÷Ϊ¾Ö²¿ÍíÆÚ»òתÒÆÐÔ·ÇÁÛ×´·ÇСϸ°û·Î°©Ò»ÏßÖÎÁÆ·½°¸µÄÁÆЧÓ밲ȫÐÔ£ºÒ»ÏîËæ»ú¡¢Ë«Ã¤¢óÆÚÁÙ´²ÊÔÑ飨InnovENT ¿¹PD-1-11Ö×ÁöѧÏîÄ¿£©

Issue JOURNAL OF THORACIC ONCOLOGY 2020, Volume 15 Issue 10 1636-1646

ÆÚ¿¯£º¡¶Ðز¿Ö×ÁöÔÓÖ¾¡·£¨JOURNAL OF THORACIC ONCOLOGY£©£¬2020 Ä꣬µÚ15¾íµÚ10ÆÚ£¬1636-1646Ò³

Author Yang Yunpeng / Wang Zhehai / Fang Jian / Yu Qitao / Han Baohui / Cang Shundong / Chen Gongyan / Mei Xiaodong / Yang Zhixiong / Ma Rui / Bi Minghong / Ren Xiubao / Zhou Jianying / Li Baolan / Song Yong / Feng Jifeng / Li Juan / He Zhiyong / Zhou Rui / Li Weimin / Lu You / Wang Yingyi / Wang Lijun / Yang Nong / Zhang Yan / Yu Zhuang / Zhao Yanqiu / Xie Conghua / Cheng Ying / Zhou Hui / Wang Shuyan / Zhu Donglei / Zhang Wen / Zhang Li

Keywords Nonsquamous NSCLC / Sintilimab / Pemetrexed / Platinum / Phase III study

Abstract

Introduction: Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCTO 3607539). Methods: A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee. Results: As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group. Conclusions: In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Cite this article as: [1]Yang Yunpeng, Wang Zhehai, Fang Jian, et al.Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11)[J].JOURNAL OF THORACIC ONCOLOGY,2020,15(10):1636-1646.

Global variations in lung cancer incidence by histological subtype in 2020: a population-based study

2020ÄêÈ«Çò·Î°©²»Í¬×é֯ѧÑÇÐÍ·¢²¡ÂʲîÒ죺һÏî»ùÓÚÈËȺµÄÑо¿

Issue LANCET ONCOLOGY 2023, Volume 24 Issue 11 1206-1218

ÆÚ¿¯£º¡¶ÁøÒ¶µ¶?Ö×Áöѧ¡·£¨LANCET ONCOLOGY£©£¬2023Ä꣬µÚ24¾íµÚ11ÆÚ£¬1206-1218Ò³

Author Zhang Yanting / Vaccarella Salvatore / Morgan Eileen / Li Mengmeng / Etxeberria Jaione / Chokunonga Eric / Manraj Shyam Shunker / Kamate Bakarou / Omonisi Abidemi / Bray Freddie

Abstract

Background Lung cancer is the second most common cancer worldwide, yet the distribution by histological subtype remains unknown. We aimed to quantify the global, regional, and national burden of lung cancer incidence for the four main subtypes in 185 countries and territories.Methods In this population-based study, we used data from Cancer Incidence in Five Continents Volume XI and the African Cancer Registry Network to assess the proportions of adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma among all lung cancers by country, sex, and age group and subsequently applied these data to corresponding national (GLOBOCAN) estimates of lung cancer incidence in 2020. Unspecified morphologies were reallocated to specified subtypes. Age-standardised incidence rates were calculated using the world standard population to compare subtype risks worldwide, adjusted for differences in age composition between populations by country. Findings In 2020, there were an estimated 2 206 771 new cases of lung cancer, with 1 435 943 in males and 770 828 in females worldwide. In males, 560 108 (39%) of all lung cancer cases were adenocarcinoma, 351 807 (25%) were squamous cell carcinoma, 163 862 (11%) were small-cell carcinoma, and 115 322 (8%) were large-cell carcinoma cases. In females, 440 510 (57%) of all lung cancer cases were adenocarcinoma, 91 070 (12%) were squamous cell carcinoma, 68 224 (9%) were small-cell carcinoma, and 49 246 (6%) were large-cell carcinoma cases. Age-standardised incidence rates for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, were estimated to be 12 center dot 4, 7 center dot 7, 3 center dot 6, and 2 center dot 6 per 100 000 person-years in males and 8 center dot 3, 1 center dot 6, 1 center dot 3, and 0 center dot 9 per 100 000 person-years in females worldwide. The incidence rates of adenocarcinoma exceeded those of squamous cell carcinoma in 150 of 185 countries in males and in all 185 countries in females. The highest age-standardised incidence rates per 100 000 person-years for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, for males occurred in eastern Asia (23 center dot 5), central and eastern Europe (17 center dot 5), western Asia (7 center dot 2), and south-eastern Asia (11 center dot 0); and for females occurred in eastern Asia (16 center dot 0), northern America (5 center dot 4), northern America (4 center dot 7), and south-eastern Asia (3 center dot 4). The incidence of each subtype showed a clear gradient according to the Human Development Index for male and female individuals, with increased rates in high and very high Human Development Index countries. Interpretation Adenocarcinoma has become the most common subtype of lung cancer globally in 2020, with incidence rates in males exceeding those of squamous cell carcinoma in most countries, and in females in all countries. Our findings provide new insights into the nature of the global lung cancer burden and facilitates tailored national preventive actions within each world region.Copyright (c) 2023 World Health Organization. Published by Elsevier Ltd. All rights reserved.

Cite this article as: [1]Zhang Yanting, Vaccarella Salvatore, Morgan Eileen, et al.Global variations in lung cancer incidence by histological subtype in 2020: a population-based study[J].LANCET ONCOLOGY,2023,24(11):1206-1218.

PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?

PI3K/Akt/mTOR ͨ·¼°ÆäÔÚ°©Ö¢ÖÎÁÆÖеÄ×÷ÓãºÎÒÃÇÊÇ·ñÈ¡µÃÁ˽øÕ¹£¿

Issue FRONTIERS IN ONCOLOGY 2022, Volume 12

ÆÚ¿¯£º¡¶Ö×ÁöѧǰÑØ¡·£¨FRONTIERS IN ONCOLOGY£©£¬2022Ä꣬µÚ12¾í

Author Peng Yan / Wang Yuanyuan / Zhou Cheng / Mei Wuxuan / Zeng Changchun

Keywords PI3K / Akt / mTOR pathway / targeted therapy / precision medicine / cancer / oncogenic alterations

Abstract

Cancer is a severe public health issue that is a leading cause of mortality globally. It is also an impediment to improving life expectancy worldwide. Furthermore, the global burden of cancer incidence and death is continuously growing. Current therapeutic options are insufficient for patients, and tumor complexity and heterogeneity necessitate customized medicine or targeted therapy. It is critical to identify potential cancer therapeutic targets. Aberrant activation of the PI3K/AKT/mTOR pathway has a significant role in carcinogenesis. This review summarized oncogenic PI3K/Akt/mTOR pathway alterations in cancer and various cancer hallmarks associated with the PI3K/AKT/mTOR pathway, such as cell proliferation, autophagy, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT), and chemoresistance. Importantly, this review provided recent advances in PI3K/AKT/mTOR inhibitor research. Overall, an in-depth understanding of the association between the PI3K/AKT/mTOR pathway and tumorigenesis and the development of therapies targeting the PI3K/AKT/mTOR pathway will help make clinical decisions.

Cite this article as: [1]Peng Yan, Wang Yuanyuan, Zhou Cheng, et al.PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?[J].FRONTIERS IN ONCOLOGY,2022,12.

Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309)

ÌæÀ×ÀûÖéµ¥¿¹ÁªºÏ»¯ÁÆ×÷Ϊ¸´·¢»òתÒÆÐÔ±ÇÑÊ°©Ò»ÏßÖÎÁÆ·½°¸£ºÒ»Ïî¶àÖÐÐÄ¢óÆÚÁÙ´²ÊÔÑ飨RATIONALE-309£©

Issue CANCER CELL 2023, Volume 41 Issue 6 1061

ÆÚ¿¯£º¡¶°©Ö¢Ï¸°û¡·£¨CANCER CELL£©£¬2023Ä꣬µÚ41¾íµÚ6ÆÚ£¬1061Ò³

Author Yang Yunpeng / Pan Jianji / Wang Hui / Zhao Yuanyuan / Qu Shenhong / Chen Nianyong / Chen Xiaozhong / Sun Yan / He Xiaohui / Hu Chaosu / Lin Lizhu / Yu Qitao / Wang Siyang / Wang Guihua / Lei Feng / Wen Jiyu / Yang Kunyu / Lin Zhixiong / Guo Ye / Chen Shaoqing / Huang Xiaoming / Wu Yanjie / Liang Liang / Chen Chenqi / Bai Fan / Ma Xiaopeng / Zhang Yun / Leaw Shiangjiin / Zhang Li / Fang Wenfeng

Abstract

Checkpoint inhibitors are effective in recurrent/metastatic nasopharyngeal cancer (R/M NPC). RATIONALE-309 (NCT03924986) randomized 263 treatment-naive R/M NPC patients to tislelizumab or placebo every 3 weeks (Q3W), plus chemotherapy (Q3W for 4-6 cycles). At interim analysis, progression-free survival (PFS) was significantly longer with tislelizumab-chemotherapy versus placebo -chemotherapy (hazard ratio: 0.52; 95% confidence interval: 0.38, 0.73; p < 0.0001). PFS benefit for tislelizumabchemotherapy versus placebo-chemotherapy was observed regardless of programmed death-ligand 1 expression. PFS after next line of treatment and overall survival showed favorable trends for tislelizumab-chemotherapy versus placebo-chemotherapy. The safety profile was similar between arms. Gene expression profiling (GEP) identified immunologically "hot"tumors, and showed an activated dendritic cell (DC) signature was associated with tislelizumab-chemotherapy PFS benefit. Our results support that tislelizumab-chemotherapy should be considered as first-line treatment for R/M NPC, and GEP and activated DC signature results may help identify patients who might benefit most from immunochemotherapy treatment.

Cite this article as: [1]Yang Yunpeng, Pan Jianji, Wang Hui, et al.Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309)[J].CANCER CELL,2023,41(6):1061.