Improvement of gefitinib-resistance of PC9/GR by thapsigargin combined with gefitinib / 药学实践与服务

Objective To study the effect and mechanism of the thapsigargin combined with gefitinib on the proliferation of human lung adenocarcinoma gefitinib resistance cell line PC9/GR. Methods The cell viability of PC9/GR treated with gefitinib alone or gefitinib combined with thapsigargin was evaluated by CCK8 assay. The flow cytometry was used to analyze the PC9/GR cell apoptosis indued by the two group drugs. The ATF-6 and IRE1α protein expression of PC9/GR cells treated with the two group drugs were detected by Western blotting. Results The group of drug combination exhibited enhanced ability to inhibit cell proliferation, promote cell apoptosis and upregulate the ATF-6 and IRE1α protein expression of the PC9/GR compared with the group gefitinib used alone. Conclusion The sensitivity of PC9/GR to gefitinib was increased when the cells were treated by thapsigargin, which may be related with the state of endoplasmic reticulum stress（ERS） induced by thapsigargin.

Analysis of Anti-tumor Innovative Drug Policy Text Based on Policy Tools in China / 医药导报

Objective By analyzing the anti-tumor innovative drug policies text in China,this study aimed to explore the focus and shortcomings of policies related to anti-tumor innovative drugs,and provide the reference for future policy formula-tion and optimization in the field of anti-tumor innovative drug.Methods By accessing the official websites of relevant minis-tries and subordinate institutions such as the Central Committee of the Communist Party of China,the State Council of the People's Republic of China,the National Health Commission of the People's Republic of China,and National Medical Products Administra-tion,and using the keywords"cancer","tumor","anti-tumor drug",and"innovative drug",etc,the national level policies related to the anti-tumor innovative drugs from January 1,2005,to December 31,2022,were collected.Based on a two-dimensional analy-sis framework of policy tools and stakeholders,the collected policy texts were classified,encoded,and statistically analyzed.Results A total of 30 policy texts were involved,and a total of 90 policy codes were generated.There were 24,43,and 23 codes for demand-based policy tools,environmental policy tools,and supply-based policy tools,accounting for 26.67%,47.78%,and 25.56%,respectively.Based on policy tools and stakeholders,a total of 183 codes were generated,with government departments,pharmaceutical enterprises,medical institutions,and patients having 70,36,54,and 23 codes respectively,accounting for 38.25%,19.67%,29.51%,and 12.57%.Conclusions China had the highest proportion of environmental policy tools in the application of innovative anti-tumor drug policies,while supply-oriented and demand-oriented policy tools were underutilized,resulting in an overall imbalance in application;The distribution pattern of stakeholders was not coordinated,with government departments and medical institutions having higher attention than pharmaceutical enterprises and patients..It was necessary to reasonably promote the collaborative application of anti-tumor innovative drug policy tools,scientifically plan the layout of anti-tumor innovative drug policy sub-tools,and balance the interests of all stakeholders to ensure the efficient implementation of the policies.

Mechanism of exosome in the pathogenesis of prostate cancer and its potential diagnostic application / 现代泌尿外科杂志

Prostate cancer (PCa) is one of the most common tumors in men.In recent years, various researches on this disease and clinical applications have benefited patients.Exosome is a subclass of extracellular vesicles (EVs).Many studies have explored the mechanisms of exosome in mediating epithelial mesenchymal transformation, angiogenesis, tumor microenvironment establishment, immune escape and drug resistance acquisition in PCa, which provides a new perspective for finding new diagnostic markers.This article reviews the role of exosome in the pathogenesis of PCa and its diagnostic application.

Research progress of B7-H3 in tumor growth,drug resistance formation and immunotherapy / 中国免疫学杂志

B7-H3(also known as CD276)is a newly discovered immune costimulatory molecule and a member of the B7 family of immune costimulatory molecules.Since the receptor of B7-H3 has not been identified yet,the specific mechanism of its immune function and intracellular signal transmission has not yet been clarified.B7-H3 is highly expressed in many malignant tumors,which indicates that not only B7-H3 can be used as a tumor marker for many malignant tumors to assist clinical diagnosis,which can be used as an effective target for tumor targeted therapy.This review mainly introduces the history of the development of the costimulatory mole-cule B7-H3 and its possible role in the development of various malignant tumors and the development of anti-tumor drug resistance,as well as the current mainstream therapeutic approaches targeting B7-H3.

Research progress on cardiovascular toxicity associated with anti-tumor drugs and its prevention and treatment / 药学学报

Cancer and cardiovascular diseases are the two major causes of death worldwide. The application of anti-tumor drugs has significantly improved the prognosis of patients, the cardiovascular toxicity caused by the application of them has become an important factor affecting the survival and prognosis of cancer patients. Therefore, the prevention and treatment of cardiovascular toxicity related to cancer treatment is increasingly important. The cardiovascular toxicity associated with anti-tumor drugs exhibits different clinical manifestations and involves multiple pathological mechanisms. This article reviews the current research progress from the perspective of the characteristics, molecular mechanisms and prevention and treatment strategies of cardiovascular toxicity caused by cancer drugs.

Research progress of sphingosine kinase and sphingosine-1-phosphate (S1P) /S1P receptor signaling in tumor microenvironment / 药学学报

Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.

Considerations on Clinical Development and Regulatory of the Oversea License-in Anti-tumor Drugs / 中国肺癌杂志

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Methodological study of rapid health technology assessment of drugs ：taking antitumor drugs as an example / 中国药房

OBJECT IVE To develop a rapid health technology assessment （rHTA）methodology of drugs based on evidence integration and value judgment ，which is suitable for China ’s national conditions. METHODS The literature review was adopted to study health technology assessment （HTA）and multi-criteria decision analysis （MCDA），and then rHTA method based on China ’s condition was formulated preliminarily with anti-tumor drugs ；the method of rHTA was demonstrated by expert consultation ； finally，the feasibility of rHTA was preliminarily verified taking the drugs for the treatment of non-small cell lung cancer as an example. RESULTS Established rHTA method combined the theory and principles of HTA and MCDA ：HTA method was used to guide the collection and synthesis of literature and real-world evidence ，while MCDA made the value measurements of achievable evidences by various stakeholders from different views ；it established the working process ，evaluation dimensions ，evaluation indicators and scoring system of rHTA. The feasibility of this method was verified by the drug example of treating non-small cell lung cancer. CONCLUSIONS A set of drug-driven rHTA methodology guidance based on HTA and MCDA is established. It can quickly collect and integrate evidence ，and provide evidence support for decision makers in a short time.

Research progress on pharmacokinetics and toxicity of vinorelbine / 中国药房

Vinorelbine（NVB）is a semisynthetic vinca alkaloid and can play an anti-tumor role by inhibiting the synthesis of tubulin. Its oral preparation has been used in the treatment of a variety of tumors as its convenience and good clinical response. The blood concentration of NVB is closely related to its curative effect and toxicity. Small variations in blood concentration may reduce the curative effect and even produce serious toxicity. There are some risks in the clinical drug use due to limited clinical data and effective pharmacodynamic monitoring methods. By reviewing the relevant literature at home and abroad ，this paper summarizes the research progress of in vivo pharmacokinetics and toxicity of NVB ，fully understands the pharmacokinetic characteristics and influencing factors of NVB ，the influencing factors of toxicity ，and the application status of pharmacokinetics in the adjustment of administration scheme ，so as to provide reference for its clinical rational use.

Research progress on anti-tumor and tumor immunity of marine natural products / 药学学报

In recent years, the oceans have provided an important source of highly promising new anti-tumor drugs for innovation and screening, with approximately 56% of biologically active compounds being discovered to have anti-tumor effects each year. In this study, we classified and summarized the approved drugs of marine origin in terms of anti-tumor therapy, and firstly, we briefly overviewed the role of the immune system in cancer pathogenesis and discussed the current dilemma of cancer immunotherapy and highlighted the main anti-tumor targets of marine drugs. Further, with a focus on tumor immunity, we classified and outlined the history of currently approved marine original drugs by species origin, structural features, relevant pathways, and clinical application and therapy. Lastly, the limitations of current marine drug research were discussed, as well as prospects and trends in new drug development.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs / 药物分析学报

Suppression of cellular O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) can repress prolifera-tion and migration of various cancer cells,which opens a new avenue for cancer therapy.Based on the regulation of insulin gene transcription,we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells.The fluorescent reporter mainly consists of a reporter (green fluorescent protein (GFP)),an internal reference (red fluorescent protein),and an operator (neuronal differentiation 1),which serves as a "sweet switch" to control GFP expression in response to cellular O-GlcNAcylation changes.The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines.Using the fluorescent reporter,we screened 120 natural products and obtained one compound,sesamin,which could markedly inhibit protein O-GlcNAcylation in HeLa and human colorectal carcinoma-116 cells and repress their migration in vitro.Altogether,the present study demonstrated the development of a novel strategy for anti-tumor drug screening,as well as for con-ducting gene transcription studies.

Research progress in multi-targeted anti-tumor natural products / 药学学报

Natural products and their derivatives are important components of anti-tumor drugs. Currently, anti-tumor drugs derived from natural products which are in clinical practice are mainly conventional cytotoxic or molecularly targeted drugs. Their application is limited by drug-related side effects and drug resistance. Recent studies have shown that anti-tumor natural products often act on multiple targets in tumor cells and in turn interfere with multiple processes in tumorigenesis and development. As tumor is a systemic disease induced by multiple factors, multi-targeted natural products possess unique potential in tumor therapy. However, the targets and mechanisms of the discovered multi-targeted antitumor natural products remain elusive, which limits their further development and application. This review summarized the research progress in the mechanism of action, target identification, and structure optimization of multi-targeted anti-tumor natural products exemplified by a few typical compounds. The research and development of these agents have also been proposed.

Knowledge, Attitudes, and Practices (KAP) Survey on the Safety of Anti-tumor Drugs in Hospital Discharge among Hospital Pharmacist / 中国药学杂志

OBJECTIVE: To analyze the knowledge, attitude and practice of hospital pharmacists on the safety of patients with anti-tumor drugs discharged from hospitals, explore possible risk factors, and provide reference for targeted guidance and rational medication of tumor patients discharged. METHODS From March 15, 2019 to May 31, 2019, pharmacists at hospitals in 31 provinces (cities) in China conducted a questionnaire survey on the safety of patients with anti-tumor drugs discharged from hospitals. RESULTS: The average score of pharmacists′ knowledges of anti-tumor drugs was 46.7, equivalent to 51.8% of the total score. Most pharmacists (74.5%) are aware of the risks of discharge of antineoplastic agents and are willing (93.9%) to provide medication guidance for cancer patients. However, the pharmacists′ guidance for patients with cancer on the discharge was mostly limited to oral presentation (62.1%), and the accessibility of pharmacists to cancer patients after discharge was generally low (55.6%). CONCLUSION: Drug safety participants pay insufficient attention to the safety risks of patients with anticancer drugs discharged, and hospital pharmacists′ knowledge reserve of anti-tumor drugs has shortcomings, there is no perfect system of medication education for discharged patients, which are all risk factors threatening the safety of medication for cancer patients after discharge. Serious efforts should be made to find solutions to continuously improve the safety of patients with anticancer drugs discharged from hospitals.

Application of single-cell sequencing technology in malignant tumor research / 中国肿瘤临床

Currently, malignant tumors are a major public health problem and pose a serious threat to human health. Because of the diversity and complexity and the high mortality rates, they have been a popular but complicated research topic for several years. Heterogeneity is one of the main characteristics of malignant tumors, and thus, this characteristic may affect many other aspects, such as tumorigenesis, development, metastasis, and therapeutic effects. With the completion of the Human Genome Project and the continuous advancement in sequencing technology, single-cell sequencing technology has been applied in many medical research fields; in particular, it is useful for analyzing tumor cell subpopulations, cell heterogeneity, tumor occurrence, evolution, and drug resistance. Therefore, this technology has provided us with a new tool for clinical diagnosis and treatment of malignant tumors and for estimating the prognosis at an early stage. In this article, we aimed to review the advances in single-cell sequencing technology and its application in malignant tumor research.

Progress in molecularly targeted anti-tumor drugs derived from natural products or their derivatives / 药学学报

Conventional chemotherapy drugs, molecularly targeted drugs, and immune checkpoint inhibitors are the major constituents of anti-tumor drugs in clinical settings at present. Molecularly targeted drugs specifically target the key proteins, genes, or signal transduction pathways in tumor cells which are essential for initiation and development of tumor, resulting in selective activity to induce cell death or growth inhibition. Molecularly targeted drugs have emerged as the mainstream in the research and development of anti-tumor drugs due to its high selectivity and low toxicity. Natural products refer to the chemical constituents or metabolites originated animals, plants, or microorganisms, which have been recognized as one of the important sources of drug discovery with abundant resources and diversified structures. At present, a number of molecularly targeted anti-tumor drugs derived from natural products or their derivatives have been approved for cancer therapy or in clinical trials. This review will summarize the molecularly targeted anti-tumor drugs derived from natural products or their derivatives according to their different cellular targets, and also outline the molecular mechanism, progress, and perspectives of these drugs.

Research Progress on Stimuli-responsive Polymer-drug Conjugates for Anti-tumor Drugs Delivery / 中国药学杂志

Polymer-drug conjugates (PDCs) have been extensively studied as nanocarriers for anti-tumor drugs delivery due to excellent stability in circulation and high drug loading ability. Stimuli-responsive PDCs(SRPDCs) could release the loading drug in response to various intra-or extracellular biological stimulis (eg, acidic pH, altered redox potential, and upregulated enzyme), as well as external artificial stimulis (eg, magnetic feld, light, temperature, and ultrasound), which are considered as "smart" nanocarriers for delivery of anti-tumor drugs. In this article, recent progresses in the development of SRPDCs for cancer therapy are reviewed, covering the design, smart linkages as well as responsive drug release property, so as to provide reference for the development of related drug delivery systems. In order to improve the successful translation of stimuli-responsive PDCs, drawbacks and limitations of current researches are discussed, besides, future perspectives and research strategies are also provided.

Application of DrugAbacus Method in Pricing Antitumor Drugs / 中国药学杂志

OBJECTIVE: China is still in its infancy in assessing the value of anti-tumor drugs, lacking a mature drug value assessment system. To provide reference for the establishment of a pharmacoeconomic model based on value assessment in China, and provide valuable reference for clinicians and patients to choose treatment options, Through the analysis and discussion of the DrugAbacus interactive calculator. METHODS: The value components and data sources of the DrugAbacus interactive calculator were analyzed by literature search, data query, etc., and the price of the anti-tumor drugs was evaluated according to the baseline values. RESULTS: The actual price of anti-cancer drug afinitor is higher than the recommended price when used to treat kidney cancer, pancreatic cancer and breast cancer. When the anti-tumor drug avastin is used in the treatment of colon cancer, the actual price is not much different from the recommended price. Halaven's suggested price is always higher than the actual price, that is, the price of the drug is at least reasonable or even low, and Ixempra's price is high, so using the drug Halaven can save more money than using the drug Ixempra. CONCLUSION: The DrugAbacus method provides a complex analysis of the factors that should be considered in drug pricing. Although there are limitations, this method reflects to a large extent the evaluation of the value of innovative drugs in society, which can provide reference for drug pricing in China.

Progress in the mechanisms of anticancer peptides / 生物工程学报

In recent years, cancer has become a major concern in relation to human morbidity and mortality. Anticancer peptides (ACPs) are the bioactive peptide with antitumor activity and found in many organisms, including mammals, amphibians, insects, plants and microorganisms. ACPs have been suggested as promising agents for antitumor therapy due to their numerous advantages over traditional chemical agents such as low molecular masses, relatively simple structures, greater tumor selectivity, fewer adverse reactions, ease of absorption, a variety of routes of administration and low risk for inducing multi-drug resistance. Combining with the related research in our group, we summarized the mechanisms of ACPs to provide some directions for research and development of peptide-based anticancer drugs.

Study on Tumor Drugs for Targeted Therapy Based on Micro-nanomotor / 中国药师

Objective:To investigate the targeted motion and controllable release of tumor drugs based on micromotor. Methods:The directional movement of Janus micro-capsules was achieved through an external magnetic field,and the controllable release of tumor drugs was induced by near-infrared laser.Results:During the same period, the movement speed of the Janus capsules micromotor was the fastest(36.8 μm·s-1,approximately equalled to 3 body length·s-1) in 15% H2O2solution. Under the control of the external magnetic field, the Janus capsules micromotor could move along the scheduled trajectory close to the area of HeLa cells. Through the irradiation of near-infrared laser, the Janus capsules micromotor was broken and released the loaded drugs quickly. Conclusion:The Janus capsule micromotor studied in the paper can be used for targeted drug delivery safely and effectively,therefore,it shows good application prospect in the field of tumor diagnosis and treatment.