Advances in targeted delivery of proteolysis targeting chimeras in cancer therapy / 生物工程学报

Small-molecule anticancer drugs inhibited tumor growth based on targeted inhibition of specific proteins, while most of oncogenic proteins are "undruggable". Proteolysis targeting chimeras (PROTAC) is an attractive and general strategy for treating cancer based on targeted degradation of oncogenic proteins. This review briefly describes the peptide-based PTOTAC and small molecule-based PROTAC. Subsequently, we summarize the development of targeted delivery of PROTAC, such as targeting molecule-mediated targeted delivery of PROTAC, nanomaterial-mediated targeted delivery of PROTAC and controllable activation of small-molecular PROTAC prodrug. Such strategies show potential application in improving tumor selectivity, overcoming off-target effect and reducing biotoxicity. At the end, the druggability of PROTAC is prospected.

Status of Inquiries to Prescribing Doctors about Cancer Chemotherapy Prescriptions by Pharmacists at an Insurance Pharmacy / 医薬品情報学

Objective: Pharmacists at insurance pharmacies play an important role in the pharmaceutical care of outpatients receiving cancer chemotherapy. This study aimed to clarify the actual status of insurance pharmacies' involvement in cancer chemotherapy and associated issues, based on an analysis of prescription inquiries made to doctors by pharmacists at an insurance pharmacy.Design: This was a retrospective observational study.Methods: The data was collected in one insurance pharmacy, which received prescriptions mainly from Gunma Prefectural Cancer Center. Among 2, 258 inquiries recorded from January 2015 to May 2018, inquires related to oral anticancer drugs or supportive care medicine were extracted. The frequency of inquiries for each item, or the frequencies of factors that lead to inquiries were calculated. Inquiries considered to have potentially led to the prevention or avoidance of adverse drug reactions (ADRs), so-called “preavoidance” inquiries, were also extracted.Results: Four hundred and forty inquiries related to 20 oral anticancer drugs were included in the analysis. The prescriptions were changed after 92.7% of all prescription inquiries. Prescription inquiries for drugs with rest periods were more frequent than those for drugs without rest periods. The most common inquiries were about the medication schedules stated on the prescription, followed by inquiries about supportive care drugs. Approximately 60% of the pharmacy inquiries were related to“pre-avoidance”inquiries. Most of the pre-avoidance inquiries concerned prevention of ADRs, though these inquiries also contributed to“reduction or avoidance of mental anxiety”. The prescription inquiries were triggered by information collected by pharmacists from patient interviews and from medication histories.Conclusion: Our findings suggest that inquiries to the prescribing doctors by pharmacists at insurance pharmacies contribute significantly to the appropriate use of anticancer drugs.

Meta-integration of medication experience and needs of oral chemotherapy drugs for cancer patients at home / 中国实用护理杂志

Objective:To systematically evaluate the medication experience and needs of patients with oral anticancer drugs at home, providing reference for the formulation and implementation of home supervision measures for these patients.Methods:PubMed, Embase, Web of Science, The Cochrane Library, CINAHL, CNKI, Wanfang database, VIP database and Chinese biomedical literature database were searched by computer to collect qualitative studies on medication experience and needs of patients with oral anticancer drugs at home. The retrieval period was from the database construction to May 1, 2021. The quality of the literature was evaluated by the Australian JBI qualitative research quality evaluation criteria for evidence-based health care centres, and the results were integrated by the pooled integration method of Meta-integration.Results:A total of 11 studies were included, 52 results were extracted, 13 categories were summarized and 4 integrated results were obtained: heavy negative psychological experience; undergo physical trials; a desire for outside support; adjust to the disease.Conclusions:According to the four aspects of experience and needs of patients with oral anticancer drugs at home, medical staff should guide them to establish health belief, improve disease perception and coping ability, and take measures to meet patients′ needs for knowledge, communication and social support through multiple channels.

Synergistic drug combination prediction in multi-input neural network / 生物医学工程学杂志

Synergistic effects of drug combinations are very important in improving drug efficacy or reducing drug toxicity. However, due to the complex mechanism of action between drugs, it is expensive to screen new drug combinations through trials. It is well known that virtual screening of computational models can effectively reduce the test cost. Recently, foreign scholars successfully predicted the synergistic value of new drug combinations on cancer cell lines by using deep learning model DeepSynergy. However, DeepSynergy is a two-stage method and uses only one kind of feature as input. In this study, we proposed a new end-to-end deep learning model, MulinputSynergy which predicted the synergistic value of drug combinations by integrating gene expression, gene mutation, gene copy number characteristics of cancer cells and anticancer drug chemistry characteristics. In order to solve the problem of high dimension of features, we used convolutional neural network to reduce the dimension of gene features. Experimental results showed that the proposed model was superior to DeepSynergy deep learning model, with the mean square error decreasing from 197 to 176, the mean absolute error decreasing from 9.48 to 8.77, and the decision coefficient increasing from 0.53 to 0.58. This model could learn the potential relationship between anticancer drugs and cell lines from a variety of characteristics and locate the effective drug combinations quickly and accurately.

Progress in Anticancer-drug Prediction Models / 中国药学杂志

In the current clinical medication, there is no method to confirm the sensitivity of patients with different genotypes to corresponding anticancer-drugs and also lack of response to side effects and drug resistance. In recent years, the development of high-throughput technology has made it possible to screen chemotherapeutic drugs on a large scale in cancer cell lines, and generated a large number of omics-data. Currently, based on these data, many predictive models of anticancer-drugs have been established, which will be helpful to predict and optimize the drug targets for cancer patients. This paper reviews the research progress of anticancer-drug prediction models.

Research advancement in natural anti-cancer product / 中国中药杂志

Human health has been severely threatened by malignant tumors continuously.Rational and effective drug use provides an effective means for the treatment of malignant tumors,and is expected to become an important way to solve the problem of tumor treatment in the future.In recent years,with the escalation of new cancer theories and the emergence of clinical drug resistance,innovative research and development of anti-cancer drugs has always been a hot spot and focus in cancer research.Among them,the discovery of novel anti-cancer drugs from natural compound is of top priority due to its strong anti-cancer efficacy and the abundant drug resources.Therefore,it is imperative to systematically summarize the cutting-edge advancements of the natural products and their potential pharmacological mechanisms according to the characteristics of tumor progression,and put forward the new directions and trends for further development of anti-cancer natural products in the future.Specifically,the research advancements on anti-cancer effect of natural products were reviewed,focusing on both the traditional and innovative application.We hope this review could bring the light on the research path of the natural anti-cancer products clearly and comprehensively,and also provide inspirations for innovative,safer and more effective anti-cancer drug development and exploration.

Awareness Survey on Handling and Exposure of Anti-Cancer Drugs among the Hospital Pharmacists / 医薬品情報学

Objective: Anticancer drugs have carcinogenic potential and are associated with occupational exposure risks among healthcareprofessionals who handle them. To minimize occupational exposure, healthcare workers must be adequately aware of the risks ofanticancer drugs and the appropriate techniques for their preparation. However, there is little information on the awareness ofpharmacists who prepare anticancer drugs in medical settings. The aim of this study was to investigate awareness of hazardous drugs(HD) and appropriate preparation techniques among pharmacists, and identify problems that pharmacists experience in managing theirexposure to anticancer drugs.Design: Questionnaire.Method: The questionnaire was sent by e-mail or mail to pharmacists employed at 270 institutions who belonged to the Chiba Societyof Hospital Pharmacists. From September 2015 to March 2016, respondents completed the questionnaires voluntarily and returnedthem by mail. Returning the questionnaire was regarded as informed consent to participate in this survey. Based on the completedquestionnaires, we examined the awareness of pharmacists in their daily work.Results: In total, 218 questionnaires were returned (collection rate: 10%). Awareness of the risks of anticancer drugs was high, and ahigh percentage of respondents use personal protective equipment during drug preparation, but the use of closed system drug transferdevices was low. Overall, however, it was found that many pharmacists had insufficient understanding of safe handling techniques.Discussion: Despite some recognition of the risks associated with exposure to HD, the measures taken to prevent exposure toHDs―including anticancer drugs―were inadequate and this issue must be urgently addressed by medical institutions and pharmacists.Countermeasures such as training sessions in the handling of HDs and the development of manuals are needed for each facility.

Development of a Novel Nonradioisotopic Assay and Cdc25B Overexpression Cell Lines for Use in Screening for Cdc25B Inhibitors

PURPOSE: The cyclin-dependent kinase 1 (Cdk1) and cyclin B complex performs important roles in the transition from the G2 to M phase in the cell cycle through removal of inhibitory phosphates on Cdk1, and Cdc25B, which is a dual-specific phosphatase, mediates these dephosphorylation events. However, measuring Cdc25B activity by existing methods is hampered by inadequate nonspecific substrates and the need to use a radiolabeled isotope. The present study aimed to develop an improved method with which to properly measure Cdc25B activity using a novel nonradioisotopic assay and Cdc25B overexpression cell lines. MATERIALS AND METHODS: A nonradioisotopic Cdk1 kinase assay, based on Western blotting for retinoblastoma protein and histone H1, was used to analyze Cdc25B activity. Also, stable Cdc25B2 and Cdc25B3 overexpression HeLa cell lines were constructed using the tetracycline-regulated expression system and were applied as a tool for screening for inhibitors of Cdc25B. RESULTS: The present study developed and optimized a nonradioisotopic assay method to properly measure Cdc25B activity. Furthermore, we constructed stable Cdc25B2 and Cdc25B3 overexpression HeLa cell lines for the establishment of a strong assay system with which to evaluate the specificity of Cdc25B inhibitors under conditions similar to the intracellular environment. These methods were confirmed as useful tools for measuring Cdc25B activity. CONCLUSION: The nonradioisotopic Cdk1 kinase assay and Cdc25B overexpression cell lines developed in this study can be conveniently used as tools for screening inhibitors of Cdc25B phosphatase as anticancer drugs.

Research Progress in New Dosage Forms of Anti-tumor Drugs for Pulmonary Administration / 中国药师

Lung cancer is one of the most common malignancies. Anti-tumor drugs with intravenous administration have systemic adverse effects as well as limited efficacy. Drugs can concentrate in lungs after pulmonary administration,which limits the distribution in the other organs and reduces the side effects of anti-tumor drugs. The paper focused on the recent progress in the studies on new dos-age forms of anti-tumor drugs for pulmonary administration for the therapy of lung cancer,so as to provide reference for the development of anti-tumor drugs for pulmonary administration.

A new mitochondria-targeted platinum complex Mor-platin inhibits HepG2 cell prolif-eration and cell invasion / 中国肿瘤临床

Objective:To investigate the effects of Mor-platin, a novel mitochondrial platinum complex, on proliferation and migration of human hepatoma carcinoma HepG2 cells. Methods:Cell counting kit-8 (CCK-8) assay was used to analyze cell proliferation of Mor-platin and classic anticancer drugs, particularly cisplatin, in HepG2 cells. A laser confocal microscope was used to observe whether Mor-platin can target mitochondria. The morphological changes in cellular mitochondria after treatment with Mor-platin were ob-served on a transmission electron microscope. Cell apoptosis was measured by flow cytometry, and cell invasion was evaluated by three-dimensional tumor spheroid model. Results:Mor-platin can inhibit cell proliferation and is dose dependent. The half inhibitory concentration (IC50) of Mor-platin is lower than that of cisplatin. Laser confocal images showed that Mor-platin can target cell mito-chondria and enrich cell mitochondria. Transmission electron microscopy images showed that cell mitochondrial morphology changed after Mor-platin treatment. Furthermore, cell mitochondrial membrane is incomplete and mitochondrial cristae are reduced. Cell apoptosis caused by Mor-platin is dose dependent. The three-dimensional tumor spheroid model showed that the cell areas of the group subjected to Mor-platin treatment are smaller than those of the control group. Conclusion:Mor-platin can target cell mitochon-dria, change the cell mitochondrial morphology, inhibit cell proliferation, and thus promote cell apoptosis. It also showed better anti-cancer effects than cisplatin. Furthermore, Mor-platin can inhibit three-dimensional tumor spheroid invasion. These results suggest that Mor-platin is a potential antitumor drug.

Plant-derived anticancer agents: A green anticancer approach

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless, plants and plant derived products is a revolutionizing field as these are Simple, safer, eco-friendly, low-cost, fast, and less toxic as compared with conventional treatment methods. Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.

Plant-derived anticancer agents: A green anticancer approach

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure.Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer.Hitherto,being effective,chemotherapy is accompanied by certain unbearable side effects.Nevertheless,plants and plant derived products is a revolutionizing field as these are Simple,safer,ecofriendly,low-cost,fast,and less toxic as compared with conventional treatment methods.Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells.Carcinogenesis is complex phenomena that involves many signaling cascades.Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners.The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals.Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy.Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors.Furthermore,drags for cancer treatment and their limitations have also been discussed.

Applications of zebrafish xenotransplantation models for in vivo evaluation of anticancer drug sensitivity test / 中国比较医学杂志

Objective To evaluate the sensitivity to 5 clinically commonly used anticancer drugs in vivo using the zebrafish xenotransplantation models of human lung cancer,stomach cancer,and liver cancer cells,respectively. Methods Zebrafish xenotransplantation models of A549 lung cancer cells,SGC-7901 stomach cancer cells and HepG2 liver cancer cells were established. The xenograft models of A549 cells were treated with three different doses of cis-platinum, paclitaxel, vinorelbine, endostar and bevacizumab, respectively. The SGC-7901 model was treated with three concentrations or doses of paclitaxel, irinotecan, hydroxyurea, cis-platinum and 5-fluorouracil, respectively. And the HepG2 model was treated with three concentrations or doses of adriamycin,gemcitabine,hydroxyurea,cis-platinum and 5-fluorouracil. The tumors were analyzed and quantified in vivo by fluorescence microscopy,and the inhibition rates of tumor growth with each drug were calculated and compared with the model control group for statistical significance. Results All of the tested anticancer drugs showed inhibitory effect on tumor cells in the zebrafish xenograft models with statistical significance in a dose-dependent manner. During the drug sensitivity test,the inhibition rate of bevacizumab on A549 lung cancer cells decreased in the order(65%)> cis-platinum(55%)> vinorelbine(40%)> endostar(39%)>paclitaxel(27%). As for the SGC-7901 stomach cancer cells, the tumor growth inhibition rate decreased in the order hydroxyurea(46%)> 5-FU(31%)= irinotecan(31%)> paclitaxel(26%)> cis-platinum(24%). And the therapeutic effect of cis-platinum on the HepG2 liver cancer cells decreased in the order(64%)> hydroxyurea(56%)>gemcitabine(46%)> adriamycin(45%)> 5-FU(38%). Conclusions Zebrafish xenotransplantation models of cancer cells are suitable for in vivo sensitivity test of anticancer drugs.

Inhibition of protein kinases by anticancer DNA intercalator, 4-butylaminopyrimido4',5':4,5thieno(2,3-)quinoline

Targeting protein kinases (PKs) has been a promising strategy in treating cancer, as PKs are key regulators of cell survival and proliferation. Here in this study, we studied the ability of pyrimido[4',5':4,5]thieno(2,3-)quinolines (PTQ) to inhibit different PKs by performing computational docking andscreening. Docking studies revealed that 4-butylaminopyrimido[4',5':4,5]thieno(2,3-)quinoline (BPTQ) has a higher order of interaction with the kinase receptors than other PTQ derivatives.screening confirms that BPTQ inhibits VEGFR1 and CHK2, with the ICvalues of 0.54 and 1.70 µmol/L, respectively. Further, cytotoxicity of BPTQ was measured by trypan blue assay. Treatment with BPTQ decreased the proliferation of HL-60 cells with an ICvalue of 12 µmol/L and induces apoptosis, as explicated by the fall in the mitochondrial membrane potential, annexin V labeling and increased expression of caspase-3. Taken together, these data suggest that BPTQ possess ability to inhibit PKs and to induce cell death in human promyelocytic leukemia cells.

La metformina como una alternativa en la prevención y tratamiento del cáncer / Metformin as an alternative for the prevention and treatment of cancer

Antecedentes: la metformina, fármaco económico y seguro, ha demostrado mejorar el pronóstico de varios tipos de cánceres. Objetivo: revisar los aspectos más relevantes de la relación entre la diabetes mellitus, la metformina y el cáncer. Desarrollo: la diabetes mellitus, en especial la tipo 2, se relaciona con algunos cánceres (mama, hígado, páncreas, ginecológico, vejiga, colon y recto), y en el sexo masculino, aumenta su recurrencia y la mortalidad. Los mecanismos responsables de esta relación no están del todo esclarecidos. La insulina y el factor de crecimiento similar a la insulina en un estado de hiperinsulinismo e insulinorresistencia, pudieran desempeñar un papel fundamental en el desarrollo de cáncer, así como otros factores de riesgo comunes a la diabetes mellitus y al cáncer (alimentación no saludable, sedentarismo, adicciones, edad, sexo, etnia y raza). La proteína liver kinase B1 se ha identificado como una proteína supresora tumoral, y al unirse con la metformina interrumpe el complejo 1 de la cadena respiratoria mitocondrial, y conduce a la disminución de la síntesis de trifosfato de adenosin, y al aumento del cociente proteína activada por mitógenos-trifosfato de adenosin en el espacio intracelular. Los quimioterápicos, esteroides y antiandrógenos, pueden afectar negativamente el metabolismo hidrocarbonado. Algunas drogas antihiperglucemiantes se han relacionado a cánceres específicos, aunque las evidencias son pobres, indirectas y controversiales. Conclusiones: la metformina pudiera utilizarse en la prevención y el tratamiento de algunos cánceres, y reducir su recurrencia y la mortalidad. Parece existir una relación entre cáncer y la diabetes mellitus, aunque muchos aspectos quedan por dilucidar, como el papel desempeñado por los fármacos anticancerígenos y antihiperglucemiantes utilizados en ambas entidades(AU)

Background: metformin, a safe inexpensive drug, has proved to improve the prognosis of several types of cancer. Objective: to review the most relevant aspects of the relationship among diabetes mellitus, metformin and cancer. Development: diabetes mellitus, particularly type 2, is related to some kinds of cancer (breast, liver, pancreas, gynecological, gallbladder, colon and rectum), and its recurrence and mortality increase in men. The mechanism behind this relationship is not fully clarified. Insulin and insulin-like growth factor under hyperinsulinism and insulin resistance conditions may play a fundamental role in developing cancer as well as other common risk factors for diabetes mellitus and cancer (unhealthy feeding, sedentary lifestyle, addictions, age, sex, ethnic group and race). Liver kinase B1 protein has been identified as tumor suppressor protein which binds the metformin to impair the mitochondrial respiratory chain complex I and leads to reduction of adenosine triphosphate synthesis and to the increase of mytogen-activated protein-adenosine triphosphate quotient in the intracellular space. Chemotherapeutic, steroid and anti-androgen drugs may negatively affect the hydrocarbon metabolism. Some antihyperglycemic drugs have been related to specific cancers, although the evidence is still poor, indirect and controversial. Conclusions: metformin may be used to prevent and treat some types of cancer and to reduce recurrence and mortality. There seems to be some relationship between cancer and diabetes mellitus, even when many aspects remain to be ascertained such as the role played by anticancer and antihyperglycemic drugs intended to treat both diseases(AU)

Twist regulation of EMT and its clinical significance in monitoring circulating tumor cells and evaluating effects of anticancer drugs / 中国肿瘤临床

Tumor cell plasticity, including epithelial to mesenchymal transition (EMT) and its reverse program, mesenchymal to epithe-lial transition (MET), regulates circulating tumor cells and carcinoma metastasis. Twist is overexpressed in rhabdomyosarcoma, breast cancer, gastric cancer, and other tumors. Twist, as a transcriptional factor, cross-talks with multiple signaling pathways, forming a com-plex network to participate in the regulation of EMT/MET in circulating tumor cells, which in turn promotes metastasis of tumor cells. Therefore, monitoring the level of Twist and epithelial–mesenchymal phenotypic molecules is important as it may be beneficial for in-creasing the detection ratio of circulating tumor cells as tumor biomarkers and for evaluating the effects of anticancer drugs.

Research progress in anticancer effects and molecular targets of honokiol in experimental therapy / 药学学报

Honokiol (HNK), one of major biological active constituents of Mangnolia officinalis, exerts a wide range of biological functions, such as moderate anticancer effects. It inhibits the growth of lung cancer, gastrointestinal cancer, head and neck squamous cell carcinoma, breast cancer, prostate cancer, ovarian cancer, in vitro and in vivo through multiple potential molecular targets. It modulates apoptosis-associated signaling pathway, inhibits growth factor receptor-mediated signal transduction pathway, blocks nuclear factor-κB signaling pathway, decreases the expression level of androgen receptors, subsides mTOR and STAT3 signaling pathway, and so on. HNK enhances the inhibitory effects of traditional anticancer drugs or targeted antitumor drugs in vitro and in vivo. It reverses multidrug resistances of cancer cells to cisplatin, doxorubicin and paclitaxol. Therefore, HNK plays a role in the augmentation of antitumor effects of cancer drugs and the reversal of multidrug resistance of tumor cells. HNK is a promising biochemical modulator of anti-cancer medicines in the cancer therapy.

Research progress of dual topoisomerase Ⅰ and Ⅱ inhibitors / 药学实践杂志

DNA topoisomerases (Tops) are essential enzymes that regulate the cellular processes such as replication , transcription ,recombination and repair .DNA Tops can be classified into two types ,topoisomerase Ⅰ (TopⅠ ) and topoi-somerase Ⅱ (TopⅡ) .They catalyze the breakage and religation of DNA ,maintaining the topological changes of DNA and va-rious DNA metabolic processes .Due to their important role in DNA metabolism ,the ability to interfere with the functions of Tops or generating Top-mediated DNA damage is an effective strategy for cancer chemotherapy .Tops have been considered as the most important targets for tumor chemotherapy .In this review ,we used examples to describe the development of dual to-poisomerase Ⅰ and Ⅱ inhibitors .

Research Progress in Polymeric Micelles Used for Tumor Targeting Drug Delivery Systems / 中国药师

Polymeric micelles as effective drug carriers have been paid wide attention. They have many considerable advantages in cancer therapy, such as high efficiency, long acting and high drug loading etc. The paper reviewed the type, preparation materials and drug lording methods of polymeric micelles, especially discussed the targeting strategy of tumor-targeting drug delivery systems and the ap-plication examples of polymeric micelles in targeting drug delivery systems.

THE CLINICAL APPLICATION OF THE MONOCLONAL ANTIBODIES TARGETED ANTI-CANCER DRUGS IN ZHONGSHAN HOSPITAL / 现代医院

Objective To know the current situation of the Monoclonal antibodies target anticancer drugs by collecting and analyzing data,to provide reference for the clinical reasonable application .Methods We collected 310 cases used the antibodies target anticancer drugs in the hospital of ZhongShan , analyzed its clinical efficacy, and evaluated the drugs'efficacy combining the time be hospitalized .Results The sum and number of charges of the Monoclonal antibodies targeted anticancer drugs are 13.67 percent and 0.12 percent in the total charges of anticancer drugs.There are 241 cases (78%) hospitalized in a single course of treatment within 14 days; 298(96%) comple-ted the chemotherapy successfully .Conclusion The monoclonal antibodies targeting anticancer drugs has the good clinical efficacy, and most of the adverse reactions are mild or moderate which can recover after treated .The key fac-tor limited the clinical application of the monoclonal antibodies targeted anticancer drugs is the price .