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Cancers have always been an intractable problem because of recurrence and drug resistance. In the past few decades, nanoparticles have been explored intensely to diagnose, prevent and treat malignancy due to their good penetrability and better targeting. However, most nanocarriers have poor biodegradation and can be discharged out of the body quickly or cleared by immune cells while failing to obtain effective drug concentration at the specific sites. The emergence of biological membrane encapsulation technology relieves the fast clearance of antitumor drugs and reduces toxicity in vivo. This review will discuss the advantages and disadvantages of several blood cell membrane-coated nanoparticles and further introduce exosome-carried drugs to evidence the promising prospect of biomimetic nanoparticle drug delivery systems.

Chunyan Luan, Baoan ChenDepartment of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province 210009, People’s Republic of ChinaCorrespondence: Baoan ChenDepartment of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, School of Medicine, Southeast University, Dingjiaqiao 87, Gulou District, Nanjing, Jiangsu Province 210009, People’s Republic of ChinaTel +86 258 327 2006Fax +86 258 327 2011Email cba8888@hotmail.comAbstract: Alkylators and nucleoside analogs were the main drugs for treatingchronic lymphoblastic leukemia (CLL), which have been replaced by monoclonal antibodies, such as rituximab in the past 10 years for refractory or relapsed CLL. The first-line immunochemotherapy regimen, rituximab combined with nucleoside analogs, significantly increased CLL patients’ first-reaction rate and improved progression-free survival. Despite the long-lasting remissions by the use of chemoimmunotherapy, most CLL patients will relapse eventually. The obinutuzumab (GA101), an updated CD20 antibody, that is thought to achieve a more durable response with unique molecular and functional characteristics. Obinutuzumab is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. This review summarizes the results of clinical studies using obinutuzumab and looks forward to its further application in treating CLL clinically.Keywords: CD20 antibody, GA101, obinutuzumab, chronic lymphocytic leukemia

Ying Du, Baoan ChenDepartment of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaAbstract: The development of drug-loading technology will bring new and rapid development to the treatment of diseases. At present, drug delivery by nanoparticles, erythrocyte, and platelet have been studied extensively. Compared with traditional anticancer drugs, nano-drugs have shown many obvious advantages, disease treatment based on nanotechnology will bring a revolution in cancer treatment. Due to its inherent biocompatibility, large drug load and long half-life in the blood circulation, erythrocyte-inspired antibiotics, and some anticancer drugs delivery systems have also entered the clinical trial stage. At present, there are relatively few studies on drug delivery by platelets as carriers. It is necessary to overcome the shortcomings of platelets, such as easy activation, deformation, thrombosis, and difficult preservation. There are many ways to combine drugs with these carriers, and each has its own advantages and disadvantages. It is necessary to seek the best combination scheme to increase drug loading and reduce the damage to therapeutic components to the carriers, so as to bring more mature and reliable methods for the clinical application of drug delivery technology. Several drug-loading technologies and their development were described according to various categories. The combination of drugs and carriers is summarized for better understanding of its practical application.Keywords: drug delivery technology, carrier, combination, tumor

Wen Bao, Ran Liu, Guohua Xia, Fei Wang, Baoan Chen Department of Hematology and Oncology, Key Medical Disciplines of Jiangsu Province, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, People’s Republic of China Background: With the development of drug delivery, novel tools and technological approaches have captured the attention of researchers in recent years. Several target drug delivery systems (DDSs) including nanoparticles (NPs) have been developed as an important strategy to deliver classical medicine. Objective: The objective of this study was to evaluate the application of novel daunorubicin (DNR)-loaded poly(lactic-co-glycolic acid)-poly-l-lysine-polyethylene glycol-transferrin (Tf) nanoparticles (DNR-loaded NPs) in hematologic malignancies in vitro and in vivo. Materials and methods: DNR-loaded NPs were prepared by the modified double-emulsion solvent evaporation/diffusion method, and its microscopic form was observed under scanning electron microscope. Intracellular distribution of DNR was directly detected by fluorescence microscopy. After establishment of a tumor xenograft model by injecting K562 cells into the left leg of nude mice, the therapeutic effect of the DNR-loaded NPs on the growth of tumors was measured by calculating the tumor size, and the relative expression of Caspase-3 protein was detected by immunohistochemical staining. Furthermore, intracellular concentration of DNR and the extent of cell apoptosis in primary leukemia cells were quantified by flow cytometry. Results: DNR-loaded NPs had a spherical shape of about 180nm in diameter. DNR-loaded NP group showed a significant enhancement of cellular uptake in K562 cells compared with DNR group. Tumor inhibition rate was higher in DNR-loaded NP group in comparison with DNR group, and the relative expression of Caspase-3 protein was upregulated in DNR-loaded NP group compared with DNR group. Furthermore, DNR-loaded NPs obviously increased intracellular concentration of DNR in primary leukemia cells compared with DNR group, but there was no significant difference in primary cell apoptosis between the two groups. These findings suggest that the novel NP DDS can enhance the performance of conventional antitumor drugs and may be suitable for further application in the treatment of hematologic malignancies. Keywords: nanoparticles, transferrin, targeted drug delivery system, leukemia

Fang Zhou, Zheng Ge, Baoan ChenDepartment of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaAbstract: Quizartinib is an effective therapy for patients with FLT3-ITD acute myeloid leukemia (AML) by continuing to inhibit the activity of FLT3 gene, leading to apoptosis of tumor cells. Multiple clinical trials have proved that it is effective in relapsed or refractory AML with an FLT3-ITD mutation. In this review, we focus on the characteristics of FLT3/ITD mutations, the mechanism and pharmacokinetics of quizartinib, and the mechanisms of resistance to quizartinib. We also summarize clinical experiences and adverse effects with quizartinib and recommend crucial approaches of quizartinib in the therapy of patients with newly diagnosed AML and patients with relapsed/refractory AML, particularly those with FLT3-ITD mutation. Quizartinib presents its advantages as a very promising agent in the treatment of AML, especially in patients with FLT3-ITD mutations. FLT3/ITD mutation can lead to constitutive autophosphorylation of FLT3 and activation of its downstream effectors including RAS/RAF/MEK, MAPK/ERK, PI3K/AKT/mTOR and JAK/STAT5 signal pathways, while Quizartinib can inhibit these downstream pathways through specific FLT3 inhibition. Quizartinib has received US Food and Drug Administration breakthrough therapy designation in patients with relapsed/refractory FLT3-ITD AML based on clinical trials. A larger sample of clinical trials are needed to verify its safety and efficacy, and the efficacy of quizartinib combined with chemotherapy or allogeneic hematopoietic cell transplantation should also be estimated in clinical trials. Meanwhile, for the side effects of quizartinib, further studies are needed to find a way to reduce its toxicity.Keywords: quizartinib, FLT3 inhibitor, FLT3-ITD mutation, AML, clinical trials, targeted therapy

Min Lin, Baoan Chen Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Abstract: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy, characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. The new drugs used for treating AML are facing a big challenge, and the candidates include cytotoxic drugs, targeted small-molecule inhibitors, and monoclonal antibodies. In recent years, active research has focused on several new agents for including them in the large antileukemic drug family. This review aims to introduce some of these new drugs and highlights new advances made in the old drugs, mainly in the last 5 years. Keywords: acute myeloid leukemia, new drug therapies, refractory/relapsed AML, 2017 NCCN guideline

Ying Du, Baoan Chen Department of Hematology and Oncology (Key Department of Jiangsu Medicine), School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China Abstract: Leukemia is a clonal malignant hematopoietic stem cell disease. It is the sixth most lethal cancer and accounts for 4% of all cancers. The main form of treatment for leukemia is chemotherapy. While some cancer types with a higher incidence than leukemia, such as lung and gastric cancer, have shown a sharp decline in mortality rates in recent years, leukemia has not followed this trend. Drug resistance is often regarded as the main clinical obstacle to effective chemotherapy in patients diagnosed with leukemia. Many resistance mechanisms have now been identified, and multidrug resistance (MDR) is considered the most important and prevalent mechanism involved in the failure of chemotherapy in leukemia. In order to reverse MDR and improve leukemia prognosis, effective detection methods are needed to identify drug resistance genes at initial diagnosis. This article provides a comprehensive overview of published approaches for the detection of MDR in leukemia. Identification of relevant MDR genes and methods for early detection of these genes will be needed in order to treat leukemia more effectively. Keywords: leukemia, multidrug resistance, MDR, detection approaches

Liting Guo,1,* Haijun Zhang,1,* Weiwei Shao,2 Baoan Chen1 1Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, 2Department of Pathology, the First People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China *These authors contributed equally tothis work Abstract: Crizotinib, the first clinically designed and synthesized as a tyrosine kinase inhibitor targeting mesenchymal–epithelial transition factor, indicating marked anticancer activity in patients with advanced, anaplastic lymphoma kinase-positive non-small-cell lung cancer, was approved by the US Food and Drug Administration in 2011. In this review, we focus on the efficacy of crizotinib compared with chemotherapy in advanced anaplastic lymphoma kinase-positive lung cancer and present the role of crizotinib as a personalized alternative in previously treated patients with non-small-cell lung cancer. Keywords: crizotinib, anaplastic lymphoma kinase rearrangement, non-small-cell lung cancer&nbsp

Runzhe Chen, Baoan Chen Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic ofChina Abstract: Siltuximab (CNTO 328) is a promising antibody-drug conjugate targeting cytokine interleukin-6 (IL-6). It is highly binding to IL-6 and thus neutralizing IL-6 bioactivity and promoting death of tumor cell. In this review, we mainly focus on the mechanisms, clinical studies, and adverse effect of siltuximab in the treatment of human malignancies. We also provide our recommendations for siltuximab treatment in the future. Keywords: interleukin-6, Castleman’s disease, clinical trials

Runzhe Chen, Baoan Chen Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China Abstract: Brentuximab vedotin is a promising antibody–drug conjugate (ADC) targeting CD30 of tumor cells. It selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells and induces tumor cell apoptosis. Various clinical trials have provided evidence that it is effective in relapsed or refractory Hodgkin’s lymphoma (HL), and it has also shown its advantages in other CD30-positive lymphomas. In this review, we focus on the structure, mechanisms, and pharmacokinetics of brentuximab vedotin. We also summarize clinical trials with brentuximab vedotin and make recommendations for brentuximab vedotin in the treatment of relapsed or refractory HL. Keywords: lymphoma, CD30-positive, clinical trials, tumor cells, antitumor effects, monoclonal antibody

Runzhe Chen, Baoan Chen Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic ofChina Abstract: Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) for chronic, blastic, or accelerated phase chronic myeloid leukemia (CML) patients who are resistant or intolerant to previous treatment. It potently inhibits BCR/ABL and SRC-family kinases (SRC, LCK, HCK, YES, FYN, FGR, BLK, LYN, FRK), as well as c-KIT, PDGFR-a and -b, and ephrin receptor kinase. Various clinical trials have provided evidence that it has more durable complete hematologic and cytogenetic responses, as well as more potency in imatinib-resistant or-intolerant CML, and it has also shown its advantages in newly diagnosed CML compared to imatinib. In this review, we mainly focus on the structure, mechanisms, pharmacokinetics, and pharmacogenetics of dasatinib. We also summarize clinical trials with dasatinib on CML and provide our recommendations for dasatinib in the treatment of CML. Keywords: imatinib, tyrosine kinase inhibitor, clinical trials&nbsp