摘要：
Cancer immunotherapy, particularly with immune checkpoint inhibitors, has revolutionized the paradigm of cancer treatment. Nevertheless, the efficacy of cancer immunotherapy remains limited in most clinical settings due to the lack of a preexisting antitumor T-cell response in tumors. Therefore, the clinical outcomes of cancer immunotherapy must be improved crucially. With increased awareness of the importance of the innate immune response in the recruitment of T cells, as well as the onset and maintenance of the T cell response, great interest has been shown in activating the cGAS-STING signaling pathway to awaken the innate immune response, thereby orchestrating both innate and adaptive immune responses to induce tumor clearance. However, tumor cells have evolved to overexpress ectonucleotide pyrophosphate phosphodiesterase 1 (ENPP1), which degrades the immunotransmitter 2',3'-cGAMP and promotes the production of immune-suppressing adenosine, resulting in inhibition of the anticancer immune response in the tumor microenvironment. Clinically, ENPP1 overexpression is closely associated with poor prognosis in patients with cancer. Conversely, depleting or inhibiting ENPP1 has been verified to elevate extracellular 2',3'-cGAMP levels and inhibit the generation of adenosine, thereby reinvigorating the anticancer immune response for tumor elimination. A variety of ENPP1 inhibitors have recently been developed and have demonstrated significant promise for cancer immunotherapy. In this review, we provide an overview of ENPP1, dissect its immunosuppressive mechanisms, and discuss the development of ENPP1 inhibitors with the potential to further improve the efficacy of cancer immunotherapy.
通讯机构：
[Tang, SS ] U;[Ning, Q] H;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;Hunan Univ Med, Sch Pharmaceut Sci, Hunan Prov Key Lab Antibody Based Drug & Intellige, Huaihua 418000, Peoples R China.;Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Peoples R China.
关键词：
RNA drug delivery system;tumor microenvironment;stimuli-responsive carrier;gene therapy
摘要：
Cancer is a significant health concern, increasingly showing insensitivity to traditional treatments, highlighting the urgent need for safer and more practical treatment options. Ribonucleic acid (RNA) gene therapy drugs have demonstrated promising potential in preclinical and clinical trials for antitumor therapy by regulating tumor-related gene expression. However, RNA's poor membrane permeability and stability restrict its effectiveness in entering and being utilized in cells. An appropriate delivery system is crucial for achieving targeted tumor effects. The tumor microenvironment (TME), characterized by acidity, hypoxia, enzyme overexpression, elevated glutathione (GSH) concentration, and excessive reactive oxygen species (ROS), is essential for tumor survival. Furthermore, these distinctive features can also be harnessed to develop intelligent drug delivery systems. Various nanocarriers that respond to the TME have been designed for RNA drug delivery, showing the advantages of tumor targeting and low toxicity. This Review discusses the abnormal changes of components in TME, therapeutic RNAs' roles, underlying mechanisms, and the latest developments in utilizing vectors that respond to microenvironments for treating tumors. We hope it provides insight into creating and optimizing RNA delivery vectors to improve their effectiveness.
摘要：
Cancer is a global public health problem. Natural polysaccharides have been shown to enhance the effectiveness of cancer treatments. Polygonatum sibiricum (PS) has been used for millennia to treat diverse diseases. PS comprises numerous active constituents, including saponins, peptides, volatile oils, polysaccharides, and lectins. Many studies have highlighted the crucial role of polysaccharides in PS. Modern studies have shown that Polygonatum sibiricum polysaccharide (PSP) exhibits diverse pharmacological activities, including immunomodulatory, antitumor, antioxidant, and anti-aging effects. However, further study of the antitumor mechanisms is difficult because the activities of PSP are closely associated with its complex structural features and the different molecular weights of its components. Therefore, this review focuses on the research background and the extraction and purification of PSP. Studies related to the mechanism of the antitumor effects of PSP constituents of different molecular weights are also summarized, and perspectives on PSP research are presented.
摘要：
This article profiles 13 newly approved nitrogen-containing heterocyclic drugs by the U.S. Food and Drug Administration (FDA) in 2023. These drugs target a variety of therapeutic areas including proteinuria in patients with IgA nephropathy, migraine in adults, Rett syndrome, PI3Kδ syndrome, vasomotor symptoms, alopecia areata, acute myeloid leukemia, postpartum depression, myelofibrosis, and various cancer and tumor types. The molecular structures of these approved drugs feature common aromatic heterocyclic compounds such as pyrrole, imidazole, pyrazole, isoxazole, pyridine, and pyrimidine, as well as aliphatic heterocyclic compounds like caprolactam, piperazine, and piperidine. Some compounds also contain multiple heteroatoms like 1,2,4-thiadiazole and 1,2,4-triazole. The article provides a comprehensive overview of the bioactivity spectrum, medicinal chemistry discovery, and synthetic methods for each compound.
通讯机构：
[Shengsong Tang] H;Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, and Institute of Pharmacy and Pharmacology, University of South China , Hengyang421001 , China<&wdkj&>Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine , Huaihua418000 , China<&wdkj&>College of Bioscience and Biotechnology, Hunan Agricultural University , Changsha 410128 , China
摘要：
Extrachromosomal DNA, referred to as extrachromosomal DNA (ecDNA), was found in most cancers and nearly absent in normal cells. The properties of ecDNA enable tumor cells to be more responsive to various environments. The non-Mendelian genetic mechanism of ecDNA could arouse increasing tumor heterogeneity. Besides, ecDNA would promote tumor invasiveness and provide resistance mechanisms associated with poorer survival consequences. Furthermore, ecDNA could profoundly impact oncogene activation, genome instability, tumor heterogeneity, etc. Consequently, they may offer potential possibilities for tumor diagnosis and therapeutics. We primarily reviewed the classification, several primary formation mechanisms, homeostasis maintenance and frontier progress of ecDNA and late emphasized its fundamental roles in tumorigenesis and put forward some new insights. We identified that miR-3168 was increased in liver CSCs and inhibited liver CSC expansion via directly targeting p53. We also illustrated that miR-3168 may predict survival benefit from TACE in HCC patients.
期刊：
International Immunopharmacology,2022年113(Pt A):109304 ISSN：1567-5769
通讯作者：
Tang, Shengsong
作者机构：
[Zhao, Jihui; Tang, Shengsong; Zeng, Luting; Zhao, Xuhong; Ning, Qian; Huang, Ruilei; Yi, Yi] Hunan Univ Med, Sch Pharmaceut Sci, Hunan Prov Key Lab Antibody Based Drug & Intellige, Huaihua 418000, Peoples R China.;[Tang, Shengsong; Ning, Qian] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Peoples R China.;[Tang, Shengsong] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Peoples R China.;[Tang, Shengsong] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构：
[Shengsong Tang] H;Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China<&wdkj&>College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, and Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China
关键词：
Cancer immunity cycle;Cancer immunotherapy;STING agonists
摘要：
Cancer immunotherapy with immune checkpoint inhibitors has achieved unprecedented success in cancer treatment; However, only a subset of patients achieved clinical benefit from this treatment, underscoring the urgent need to identify new strategies to enhance the clinical efficacy of immune checkpoint inhibitors. Given the essential role of innate immunity in cancer immune surveillance, tremendous effort has been focused on the innate immune pathways that can be pharmacologically modulated to improve the clinical outcome of checkpoint inhibitors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays essential roles in host defense against cancers. Activation of the cGAS-STING signaling pathway induces the expression of type I interferons and proinflammatory cytokines, culminating in promotion of a robust adaptive antitumor immunity. As part of this innate immune signaling pathway, STING is ubiquitously expressed in immune and nonimmune cells. STING activation has been demonstrated to propagate the cancer immunity cycle, remodel the tumor microenvironment, and ultimately eliminate tumor cells. The immunomodulatory roles of STING enable it to be an appealing target for cancer immunotherapy. As such, STING agonists that are capable of triggering antitumor immune responses have been developed in recent years, and several of them have advanced into clinical trials. In this review, we first give an overview on the STING signaling pathway, then dissect the roles of STING activation in different steps of the cancer immunity cycle and finally discuss the development of STING agonists as well as challenges with STING activation, with the potential to make cancer immunotherapy with STING agonists more effective.
期刊：
International Immunopharmacology,2022年106:108597 ISSN：1567-5769
通讯作者：
Zhizhong Xie<&wdkj&>Shengsong Tang
作者机构：
[Xie, Zhizhong; Niu, Dun; Wu, Yiwen; Lei, Ziyao; Zhang, Ming] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Xie, Zhizhong; Niu, Dun; Wu, Yiwen] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Peoples R China.
通讯机构：
[Zhizhong Xie] I;[Shengsong Tang] H;Hunan Province Key Laboratory for Antibody-based Drug and Intelligent Delivery System, Hunan University of Medicine, Huaihua 418000, China<&wdkj&>Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China
摘要：
Warburg effect is one of the hallmarks of tumor favoring the suppression of normal oxidative phosphorylation (OxPhos) and the adaptation to hypoxia. In addition to providing continuous energy to meet the demands of tumors, accelerated Warburg effect also produces a large amount of lactic acid. Lactic acid shuttles between different cell populations within the tumor microenvironment (TME) and confers tumor cells to interact with surrounding cells, which has emerged as a new phenomenon in the field of tumor biology and tumorigenesis. Lactic acid not only fulfills the energetic demands of stromal cells, but becomes a major regulator of their activity by serving as a signaling molecule. Activated stromal cells in turn support tumor development. In this review, we discuss the role of lactic acid in transformation and oncogenic function of stromal cells including fibroblasts, macrophages, adipocytes and vascular endothelial cells, and suggest the relevance of lactic acid in therapy response and essential questions in this field.
通讯机构：
[Shengsong Tang] H;Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, and Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China<&wdkj&>Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China<&wdkj&>College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
摘要：
Aging is a natural physiological process, but aging can increase the prevalence and mortality of chronic diseases in the elderly. It involves multiple organs and systems, and an essential aspect of aging is immunosenescence. With the increase of age, the immune system has undergone a series of changes and disorders. These changes have led to a decline in the resistance of the elderly to infection, reduced immunity to vaccines, increased incidence of cancer and autoimmune diseases, and an increased structural prevalence of low-grade inflammation. Moreover, affecting the aging process to a certain extent. This review introduces the changes in the immune system during aging and discusses the consequences and effects of these changes. And its effect on the aging process and the methods and ways of anti-aging were discussed.
作者机构：
[Lei, Xiaoyong; Tang, Shengsong; Xing, Jichen] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;[Lei, Xiaoyong; Tang, Shengsong; Xing, Jichen] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Tang, Shengsong; Xing, Jichen; Ning, Qian] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua, Peoples R China.;[Tang, Diya] Cent South Univ, Dept Med Oncol, Xiangya Hosp, Changsha, Peoples R China.;[Mo, Zhongcheng] Guilin Med Univ, Coll Basic Med, Inst Basic Med Sci, Guilin, Guangxi, Peoples R China.
通讯机构：
[Tang, Shengsong] U;Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
drug resistance;extrachromosomal DNA;oncogene amplification;tumor heterogeneity
摘要：
The amplification of oncogenes on extrachromosomal DNA (ecDNA) provides a new mechanism for cancer cells to adapt to the changes in the tumor microenvironment and accelerate tumor evolution. These extrachromosomal elements contain oncogenes, and their chromatin structures are more open than linear chromosomes and therefore have stronger oncogene transcriptional activity. ecDNA always contains enhancer elements, and genes on ecDNA can be reintegrated into the linear genome to regulate the selective expression of genes. ecDNA lacks centromeres, and the inheritance from the parent cell to the daughter cell is uneven. This non-Mendelian genetic mechanism results in the increase of tumor heterogeneity with daughter cells that can gain a competitive advantage through a large number of copies of oncogenes. ecDNA promotes tumor invasiveness and provides a mechanism for drug resistance associated with poorer survival outcomes. Recent studies have demonstrated that the overall proportion of ecDNA in tumors is approximately 40%. In this review, we summarize the current knowledge of ecDNA in the field of tumorigenesis and development.
期刊：
Journal of Drug Targeting,2021年29(7):703-715 ISSN：1061-186X
通讯作者：
Xianhui Zhang<&wdkj&>Linxi Chen
作者机构：
[Tang, Shengsong; Zhou, Qun] Hunan Univ Med, Sch Pharmaceut Sci, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua, Peoples R China.;[Zhang, Xianhui] Dongkou Peoples Hosp, Orthoped Dept, Dongkou 422300, Hunan, Peoples R China.;[Chen, Linxi] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hunan Prov Cooperat Innovat Ctr Mol Target, New Drug Study,Inst Pharm & Pharmacol, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xianhui Zhang] O;[Linxi Chen] H;Orthopedics Department, Dongkou People’s Hospital, Dongkou, China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target, New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China
期刊：
International Immunopharmacology,2020年86:106700 ISSN：1567-5769
通讯作者：
Tang, Shengsong
作者机构：
[Tang, Sha; Tang, Shengsong; Yang, Ling] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;[Tang, Sha; Tang, Shengsong; Yang, Ling] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Tang, Sha; Tang, Shengsong; Yang, Ling; Ning, Qian] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Peoples R China.;[Mo, Zhongcheng] Guilin Med Univ, Coll Basic Med, Inst Basic Med Sci, Guilin 541199, Guangxi, Peoples R China.
通讯机构：
[Tang, Shengsong] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Peoples R China.
关键词：
Cancer immune cycle;Immune checkpoint;Immune escape;Immunotherapy
摘要：
Cancer is a critical issue globally with high incidence and mortality, imposing great burden on the society. Although great progress has been made in immunotherapy based on immune checkpoint, only a subset of patients responds to this treatment, suggesting that cancer immune evasion is still a major barrier in current immunotherapy. There are a series of factors contributing to immune evasion despite in an immunocompetent environment. Given that these factors are involved in different steps of the cancer immune cycle. In this review, we discuss the mechanisms of immune escape in each step of the cancer immune cycle and then present therapeutic strategies for overcoming immune escape, with the potential to better understand the determinants of immune escape and make anti-tumor immunity more effective.
摘要：
With the arrival of the precision medicine and personalized treatment era, targeted therapy that improves efficacy and reduces side effects has become the mainstream approach of cancer treatment. Antibody fragments that further enhance penetration and retain the most critical antigen-specific binding functions are considered the focus of research targeting cancer imaging and therapy. Thanks to the superior penetration and rapid blood clearance of antibody fragments, antibody fragment-based imaging agents enable efficient and sensitive imaging of tumour sites. In tumour-targeted therapy, antibody fragments can directly inhibit tumour proliferation and growth, serve as an ideal carrier for delivery of anti-tumour drugs, or manipulate the immune system to eliminate tumour cells. In this review, the excellent physicochemical properties and the basic structure of antibody fragments are expressly depicted depicted, the progress of antibody fragments in cancer therapy and imaging are thoroughly summarized, and the future development of antibody fragments is predicted.
摘要：
Polymeric micelles (PMs) play a vital role in multidrug co-delivery and cancer treatment. However, the development of intelligent PMs further allows PMs to accurately -target tumour, selectively release cargo multidrug and increase uptake. Therefore, targets, controlled release and uptake of intelligent PMs should be paid more attention to improvement synergistic therapeutic outcomes and minimize side effects. In this review, tumour targeting of co-delivery intelligent PMs and its intracellular trafficking mechanisms were overviewed. And this review provides a comprehensive summarization of several intelligent co-delivery PMs. Such a system could control the multidrug to be released simultaneously or sequentially by special properties of tumour microenvironment (TME) (including acidic PH, redox, overexpressed enzyme, excessive temperature) and external environment trigger. Additionally, limitations, clinical translation and future perspectives of intelligent co-delivery PMs were also being discussed in this article.
作者机构：
[Tang, SS; Mo, Zhongcheng; Ou, Hanxiao; Tang, Shengsong; Liu, Chuhao; Xiao, Xinwen; Feng, Wenjie] Univ South China, Inst Pharm & Pharmacol, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Ctr Life Sci, Huaihua 418000, Peoples R China.;[Liu, Chuhao; Xiao, Xinwen; Feng, Wenjie] Univ South China, Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Tang, SS; Mo, ZC] U;[Tang, Shengsong] H;Univ South China, Inst Pharm & Pharmacol, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;Hunan Univ Med, Ctr Life Sci, Huaihua 418000, Peoples R China.
关键词：
adenosine monophosphate-activated protein kinase;autophagy;lipid metabolism;atherosclerosis-associated cell;atherosclerosis
摘要：
Atherosclerosis is characterized by the accumulation of lipids and deposition of fibrous elements in the vascular wall, which is the primary cause of cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism that regulates multiple physiological processes, including lipid and glucose metabolism and the normalization of energy imbalances. Overwhelming evidence indicates that AMPK activation markedly attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and inflammation and promotes cholesterol efflux and efferocytosis. Physiological autophagy is essential for maintaining normal cardiovascular function. Increasing evidence demonstrates that autophagy occurs in developing atherosclerotic plaques. Emerging evidence indicates that AMPK regulates autophagy via a downstream signaling pathway. The complex relationship between AMPK and autophagy has attracted the attention of many researchers because of this close relationship to atherosclerosis development. This review demonstrates the role of AMPK and autophagy in atherosclerosis. An improved understanding of this interrelationship will create novel preventive and therapeutic strategies for atherosclerosis.
摘要：
Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer deaths among females in underdeveloped countries. This study aimed to identify several novel cervical cancer-specific targeting peptides (CSPs) to provide new methods for the effective diagnosis and treatment of cervical cancer. Peptide library screening in vivo was performed on human cervical cancer xenografts with Ph.D.™-12 and C7C phage display peptide libraries. Two specific peptide sequences (GDALFSVPLEVY and KQNLAEG), which were enriched in tumors, were screened, and respectively, named CSP-GD and CSP-KQ through three rounds of biopanning. The in vivo tumor-targeting ability of these peptides was identified by injecting them into mice with cervical cancer xenograft. CSPs were compounded and labeled with fluorescein isothiocyanate (FITC). The specificity and affinity of FITC-CSPs were evaluated in human cervical cancer cell lines and tissue microarrays in vitro by immunofluorescent staining. Results showed that FITC-CSP-GD and FITC-CSP-KQ evidently and specifically bound to the cell membrane and cytoplasm of SiHa, ME-180, and C-33A cells in vitro. In human cervical cancer tissue, FITC-CSP-GD and FITC-CSP-KQ strongly targeted human cervical adenocarcinoma and cervical squamous cell carcinoma tissues, respectively. A bright FITC signal was located mainly on the cell membrane and cytoplasm of tumor cells. In conclusion, the novel 12-residue peptide CSP-GD and 7-residue peptide CSP-KQ could specifically target human cervical cancer and may have the potential to be used in the diagnosis and targeted therapy of cervical cancer.
