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Insights on liver-directed surgical innovations, targeted therapies, and immunotherapy for biliary tract cancer: navigating the new European Society for Medical oncology (ESMO) Clinical Practice Guidelines

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 516-519页

作者： Ajay V.Maker Division of Surgical oncology Department of SurgeryUniversity of CaliforniaSan FranciscoCAUSA

Cancers of the bile duct,including gallbladder cancer,extrahepatic cholangiocarcinoma,hilar and intrahepatic cholangiocarcinoma,present a significant treatment *** by their notorious difficulty to diagnose or biopsy,intricate anatomical locations and diverse clinical presentations,these malignancies collectively contribute to a significant burden on global *** epidemiology of bile duct cancers reveals worldwide variations in incidence,prevalence,and mortality rates,emphasizing the need for a nuanced understanding of each subtype and the local environmental *** in early diagnosis further compound the complexity of managing these cancers,often leading to advanced stage at the time of detection and treatment *** remains the cornerstone of curative-intent treatment of bile duct cancers,yet the rate of recurrence and metastases underscores the importance of comprehensive multidisciplinary therapeutic *** randomized clinical trials have been performed;however,they have been challenged by the lack of active agents,a limited number of accrued patients,and a grouping of all patients together regardless of where in the biliary tract the tumor *** has resulted in variations in treatment strategies and multiple treatment options that range from immunotherapy to radiation to hepatic artery infusion therapy(more on this later).A greater understanding of the mutational landscape of biliary tract cancers has resulted in optimism around appropriately targeted agents and combination ***,many of these regimens await robust outcomes data,and it is questionable if they significantly move the needle forward to improve overall *** now,more than ever,there is a need for updated treatment guidelines.

关键词： Gallbladder cancer cholangiocarcinoma guidelines bile duct cancer hepatic artery infusion pump

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Quality assessment of surgery for colorectal cancer:Where do we stand?

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 982-987页

作者： Stefan Morarasu Cristian Livadaru Gabriel-Mihail Dimofte The Second Department of Surgical oncology Regional Institute of OncologyIasi 707483Romania

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past *** has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units *** mesorectal excision,complete mesocolic excision(CME),and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical ***,there are still ongoing discrepancies in outcomes largely based on surgeon *** is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume *** markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional *** the evolution of CME surgery,various quality markers have been described,mostly based on measurements on the surgical specimen and lymph node yield,while others have proposed radiological markers(*** stumps)measured on postoperative scans as part of the routine cancer *** is no ideal marker;however,taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

关键词： Colorectal cancer Colon surgery Arterial stump Complete mesocolic excision Surgical quality

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The Chinese Society of Clinical oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

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Cancer Communications 2024年第1期44卷 127-172页

作者： Feng-Hua Wang Xiao-Tian Zhang Lei Tang Qi Wu Mu-Yan Cai Yuan-Fang Li Xiu-Juan Qu Hong Qiu Yu-Jing Zhang Jie-Er Ying Jun Zhang Ling-Yu Sun Rong-Bo Lin Chang Wang Hao Liu Miao-Zhen Qiu Wen-Long Guan Sheng-Xiang Rao Jia-Fu Ji Yan Xin Wei-Qi Sheng Hui-Mian Xu Zhi-Wei Zhou Ai-Ping Zhou Jing Jin Xiang-Lin Yuan Feng Bi Tian-Shu Liu Han Liang Yan-Qiao Zhang Guo-Xin Li Jun Liang Bao-Rui Liu Lin Shen Jin Li Rui-Hua Xu Department of Medical oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Gastrointestinal oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijingP.R.China Department of Radiology Peking University Cancer HospitalBeijingP.R.China Department of Endoscopy Center Peking University Cancer HospitalBeijingP.R.China Department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhouGuangdongP.R.China Department of Gastric Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Medical oncology The First Hospital of China Medical UniversityShenyangLiaoningP.R.China Department of Medical oncology Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Radiotherapy Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Medical oncology Zhejiang Cancer HospitalHangzhouZhejiangP.R.China Department of Medical oncology Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiP.R.China Department of Surgical oncology The Fourth Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangP.R.China Department of Medical oncology Fujian Cancer HospitalFuzhouFujianP.R.China Tumor Center The First Hospital of Jilin UniversityChangchunJilinP.R.China Department of General Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Department of Radiology Zhongshan HospitalFudan UniversityShanghaiP.R.China Department of

The 2023 update of the Chinese Society of Clinical oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision *** updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer *** revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric *** advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)***,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric *** 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

关键词： Chinese Society of Clinical oncology(CSCO) gastric cancer diagnosis surgery neoadjuvant adjuvant radiotherapy chemotherapy targeted therapy immunotherapy

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Immune checkpoint inhibitors break whose heart? Perspectives from cardio-immuno-oncology

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Genes & Diseases 2024年第2期11卷 807-818页

作者： Yingying He Hui Yu Shuang Dai Miao He Ling Ma Zihan Xu Feng Luo Li Wang oncology Department Deyang People's HospitalDeyangSichuan 618000China Department of Medical oncology Lung Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610000China Cardiovascular Department Mianyang Central HospitalMianyangSichuan 621000China Department of Rheumatology and Immunology Deyang People's HospitalDeyangSichuan 618000China

Immune checkpoint inhibitors (ICIs) are monoclonal antibody antagonists,which can block cytotoxic T lymphocyte antigen-4 (CTLA-4),programmed death-1/ligand-1 (PD-1/PD-L1) pathways,and other molecules exploited by tumor cells to evade T cell-mediated immune *** have transformed the treatment landscape for various cancers due to their amazing *** anti-tumor therapies,including targeted therapy,radiotherapy,and chemotherapy,combine ICIs to make the treatment more ***,the off-target immune activation caused by ICIs may lead to a broad spectrum of immune-related adverse events (irAEs) affecting multiple organ *** irAEs,cardiotoxicity induced by ICIs,uncommon but fatal,has greatly offset survival benefits from ICIs,which is heartbreaking for both patients and ***,such cardiotoxicity requires special vigilance,and it has become a common challenge both for patients and *** article reviewed the clinical manifestations and influence of cardiotoxicity from the view of patients and clinicians,elaborated on the underlying mechanisms in conjunction with animal studies,and then attempted to propose management strategies from a cardio-immuno-oncology multidisciplinary perspective.

关键词： Cancer management Cardio-immuno-oncology multidisciplinary Cardiotoxicity Immune checkpoint inhibitors Immune tolerance

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Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis

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Chinese Journal of Natural Medicines 2024年第6期22卷 554-567页

作者： LI Weiming GAO Ming XUE Weili LI Xiaoli CHANG Yu ZHANG Kaixin WEN Chenyu ZHANG Mingzhi Department of oncology Henan University of Traditional Chinese MedicineZhengzhou 450000China Department of oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China

Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment *** acid(PA)has shown promising antitumor *** study aims to elucidate the molecular mechanisms by which PA influences DLBCL *** quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell *** were made of cell viability,apoptosis,and autophagy-related protein expression following PA *** analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell *** efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse ***-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control *** treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of *** luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 *** experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 *** vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 *** acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.

关键词： Palmitic acid Diffuse large B-cell lymphoma MiR-429 DNMT3A FOXO1 Autophagy

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Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

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Biomedical and Environmental Sciences 2024年第6期37卷 581-593页

作者： Nani Li Xiaoting Qiu Jingsong Xue Limu Yi Mulan Chen Zhijian Huang Department of Medical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina Department of Breast Surgical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina Departmen of Pathology Shenzhen Longhua Maternity and Child Healthcare HospitalShenzhen 518109GuangdongChina

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment ***8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing *** leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to *** Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC *** the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T ***,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic *** accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)***,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic ***,we investigated the potential underlying biological pathways that contribute to divergent treatment *** We successfully developed a model capable of predicting the prognosis of patients with *** areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,*** this risk model,we stratified the samples into high-and low-risk *** KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine ***,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that o

关键词： Breast Cancer Immunotherapy Prognosis CD8+T cells PD-L1

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Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

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Chinese Journal of Integrative Medicine 2024年第1期30卷 85-95页

作者： JIAO Ju-ying CHENG Chien-shan CAO Zhang-qi CHEN Lian-yu CHEN Zhen Department of Integrative oncology Fudan University Shanghai Cancer CenterShanghai(200032)China Department of oncology Shanghai Medical CollegeFudan UniversityShanghai(200032)China

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

关键词： cancer Chinese medicine syndrome ZHENG dampness-heat syndrome animal model pancreatic tumor evaluation methods

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Targeting RAF dimers in RAS mutant tumors:From biology to clinic

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1895-1923页

作者： Huanhuan Yin Qiulin Tang Hongwei Xia Feng Bi Division of Abdominal Cancer Department of Medical OncologyCancer Center and Laboratory of Molecular Targeted Therapy in OncologyWest China HospitalSichuan UniversityChengdu 610041China

RAS mutations occur in approximately 30%of tumors worldwide and have a poor prognosis due to limited *** targeting of KRAS G12C has achieved significant success in recent years,but there is still a lack of efficient therapeutic approaches for tumors with non-G12C KRAS mutations.A highly promising approach is to target the MAPK pathway downstream of RAS,with a particular focus on RAF ***-generation RAF inhibitors have been authorized to treat BRAF mutant tumors for over a ***,their use in RAS-mutated tumors is not recommended due to the paradoxical ERK activation mainly caused by RAF *** address the issue of RAF dimerization,type II RAF inhibitors have emerged as leading *** clinical studies have shown the initial effectiveness of these agents against RAS mutant ***,type II RAF inhibitors in combination with MEK or ERK inhibitors have demonstrated impressive efficacy in RAS mutant *** review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treatment in tumors with RAS mutations,as well as recent progress in therapeutic approaches to address the problem of RAF dimerization in RAS mutant tumors.

关键词： RAS mutations RAF dimerization RAF inhibitors Cancer therapy Drug resistance

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FGFR3 alterations in bladder cancer:Sensitivity and resistance to targeted therapies

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Cancer Communications 2024年第10期44卷 1189-1208页

作者： Maxim Noeraparast Katarina Krajina Renate Pichler Dora Nieders-Beke Shahrokh F Shariat Viktor Grünwald Sascha Ahyai Martin Pichler Translational oncology II.Med Clinics Hematology and OncologyAugsburgGermany Department of Urology Medical University of InnsbruckInnsbruckAustria Department of Hematology and oncology Clinics OttakringViennaAustria Department of Urology Medical University of ViennaViennaAustria Interdisciplinary Genitourinary oncology Clinic for UrologyClinic for Medical OncologyUniversity Hospital EssenHufelandstrase 55EssenGermany Department of Urology Medical University of GrazGrazAustria

In this review,we revisit the pivotal role of fibroblast growth factor receptor 3(FGFR3)in bladder cancer(BLCA),underscoring its prevalence in both nonmuscle-invasive and muscle-invasive forms of the ***3 mutations in up to half of BLCAs play a well-established role in tumorigenesis,shaping distinct tumor initiation patterns and impacting the tumor microenvironment(TME).Emphasizing the importance of considering epithelial-mesenchymal transition profile and TME status,we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3-mutated *** writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3-mutated BLCA,stressing the pressing need to unravel resistance mechanisms and identify co-targets for future combinatorial studies.A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms,including secondarymutations,epigenetic alterations in pathway effectors,phenotypic heterogeneity,and population-specific variations within FGFR3 mutational ***,we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3-mutated BLCA.

关键词： Bladder Cancer Erdafitinib FGFR inhibition FGFR3 mutations Resistance to Erdafitinib Tumor Microenvironment

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Microbiota in colorectal cancer related to liver metastasis

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Chinese Journal of Cancer Research 2024年第1期36卷 17-24页

作者： Peijun Wei Weiming Han Zitong Zhang Xue Tian Chen Yang Qiaoxuan Wang Weihao Xie Ying Liu Yuanhong Gao Hui Chang Department of Radiation oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Guangdong Provincial Clinical Research Center for Cancer Guangzhou 510060China Sun Yat-sen University Cancer Center Guangzhou 510060China Department of Pediatric oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of ***, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

关键词： Gut microbiota liver metastasis colorectal cancer

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