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New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER Division of oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for Hematology and oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment immunotherapy Gene expression Omics

molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

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World Journal of Gastroenterology 2024年第13期30卷 1815-1835页

作者： Samantha Sharma Naresh Singh Anita Ahmed Turk Isabella Wan Akshay Guttikonda Julia Lily Dong Xinna Zhang Mateusz Opyrchal Department of Medical and molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States Division of Hematology/oncology Department of MedicineIndiana University School of MedicineIndianapolisIN 46202United States Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202United States

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

关键词： Colorectal cancer Immune checkpoint inhibitors Clinical trials immunotherapy Microsatellite instability Microsatellite stability DNA mismatch repair

A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine

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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng Rex C.Haydon Hue H.Luu Russell R.Reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China molecular oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma

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Chinese Journal of Cancer Research 2024年第2期36卷 195-214页

作者： Sana Rashid Yingchuan Sun Umair Ali Khan Saddozai Sikandar Hayyat Muhammad Usman Munir Muhammad Usman Akbar Muhammad Babar Khawar Zhiguang Ren Xinying Ji Malik Ihsan Ullah Khan Institute of molecular Biology and Biotechnology University of LahoreLahore 54590Pakistan Department of Internal oncology(section Ⅰ) Xuchang Municipal Central HospitalXuchang 461000China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Australian Institute for Bioengineering&Nanotechnology the University of QueenslandBrisbane 4072Australia Gomal Center of Biochemistry and Biotechnology Gomal UniversityDera Ismail Khan 29111Pakistan Applied molecular Biology and Biomedicine Lab Department of ZoologyUniversity of NarowalNarowal Punjab 51600Pakistan Kaifeng Municipal Key Laboratory for Infection and Biosafety Henan International Joint Laboratory of Nuclear Protein RegulationSchool of Basic Medical SciencesHenan UniversityKaifeng 475004China Faculty of Basic Medical Subjects Shu-Qing Medical College of ZhengzhouZhengzhou 450064China Department of Medicine Huaxian County People's HospitalHuaxian 456400China

Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

关键词： Hepatocellular carcinoma circulating tumor DNA biomarkers single nucleotide variations diagnosis prognosis

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 medicine.These updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer patients.Key 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 cancer.For 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)patients.Additionally,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer.The 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

Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal Medical oncology Fudan University Shanghai Cancer CenterShanghai 200032China Precision Cancer Medical Center Affiliated with Fudan University Shanghai Cancer Center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide1.Surgical radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of surgery2.Fortunately,the transformation of high-throughput sequencing has accelerated the development of precision medicine.For example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in CRC3.Furthermore,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

Boosting synergism of chemo- and immunotherapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

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Acta Pharmaceutica Sinica B 2024年第2期14卷 836-853页

作者： Ge Song Minghui Li Shumin Fan Mengmeng Qin Bin Shao Wenbing Dai Hua Zhang Xueqing Wang Bing He Qiang Zhang Beijing Key Laboratory of molecular Pharmaceutics and New Drug Delivery Systems School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Medical oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijing 100142China

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel the value of this classical therapeutic strategy.Here,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic drugs.Alendronate in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle core.The synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic mechanism.Differing from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy.Therefore,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

关键词： Bisphosphonate coordinationlipid nanogranules Ferroptosis Mevalonatemetabolism Mitochondrial metabolism Nano-systematic biology

CD5:from antiquated T cell marker to immunotherapy’s new hope

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2442-2444页

作者： Sandra Schwarz Michael Linnebacher molecular oncology and immunotherapy Clinic of General SurgeryRostock University Medical Center18057RostockGermany

In a recent study published in Science,He et al.investigated the role of CD5 on dendritic cells(DCs)in priming effector T cells.^(1)By proving the importance of CD5 in engaging effective antitumor immune responses,the... 详细信息

关键词： immunotherapy al. CD5

Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

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oncology Research 2024年第7期32卷 1141-1162页

作者： PAULINA CHMIEL ALEKSANDRA SŁOWIKOWSKA ŁUKASZ BANASZEK ANNA SZUMERA-CIEĆKIEWICZ BARTŁOMIEJ SZOSTAKOWSKI MATEUSZ J.SPAŁEK TOMASZŚWITAJ PIOTR RUTKOWSKI ANNA M.CZARNECKA Department of Soft Tissue/Bone Sarcoma and Melanoma Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland Faculty of Medicine Medical University of WarsawWarsaw02-091Poland Department of Pathology Maria Sklodowska Curie National Research Institute of OncologyWarsaw02-781Poland Department of Radiotherapy Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland

Inﬂammatory myoﬁbroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging features.However,IMT is identiﬁed by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows conﬁrmation of the diagnosis.While surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difﬁcult to deﬁne.Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT.Crizotinib,an ALK tyrosine kinase inhibitor(TKI),was ofﬁcially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK rearrangement.However,most patients face resistance and disease progression,requiring consideration of sequential treatments.Combining radiotherapy with targeted therapy appears to be beneﬁcial in this indication.Early promising results have also been achieved with immunotherapy,indicating potential for combined therapy approaches.However,deﬁned recommendations are still lacking.This review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.

关键词： Inﬂammatory myoﬁbroblastic tumor(IMT) Epithelioid inﬂammatory myoﬁbroblastic sarcoma Tyrosine kinase inhibitors(TKI) Anaplastic lymphoma kinase(ALK)