Research progress of immune checkpoint agonist for solid tumor treatments / 国际肿瘤学杂志

Immune checkpoint consists of inhibitory and stimulatory molecules. Drugs blocking inhibitory checkpoint programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) are currently utilized for wide variety of human cancers. Agonists of stimulatory checkpoints such as GITR, OX40, 4-1BB, ICOS, CD40 and STING are undergoing critical clinical trials. Immune checkpoint agonists that affect stimulatory checkpoint molecules develop rapidly, and immune agonist antibodies thus represent an important approach for solid tumor treatments.

Recent Insights into Mechanisms Governing Breast Cancer Dormancy / 肿瘤防治研究

Tumor dormancy refers to the status of disseminated cancer cells that remain in a viable yet not proliferating state for a prolonged period. Dormant cells will eventually "re-awake" resume their proliferation, and produce overt metastasis. The dormancy mechanism of cancer has attracted attention because of the close relationship between late recurrence and tumor dormancy. In this review, we illustrate the latest discoveries on the biological underpinnings of breast cancer dormancy and offer clinicians an overview of dormancy in breast cancer to guide them in the basic understanding of the complexity that underlies this process.

Expression and Clinical Significance of m6A Methylatransferase ZC3H13 in Gastric Cancer Tissues and Serum / 肿瘤防治研究

Objective To investigate the expression of m6A methylatransferase ZC3H13 in tissues and peripheral blood of patients with gastric cancer and its application value in gastric cancer. Methods UALCAN and GEPIA databases were used to analyze the expression difference of ZC3H13 in gastric cancer and adjacent normal tissues at transcription level; GEPIA and Kaplan-Meier Plotter databases were used to analyze the correlation between ZC3H13 expression level and OS of gastric cancer patients.ELISA was used to determine the concentration of ZC3H13 in 80 newly-diagnosed gastric cancer patients and 50 healthy controls, and to analyze its relation with clinicopathological data; IHC method was used to detect the expression level of ZC3H13 in 74 cases of cancer tissues and 40 cases of unpaired paracancerous tissues, and to analyze its relation with clinicopathological data. Results The expression of ZC3H13 in gastric cancer tissues was significantly higher than that in adjacent gastric tissues (P < 0.05).The positive rate of ZC3H13 protein in gastric cancer tissues was significantly higher than that in adjacent normal tissues (74.3%vs.52.5%, P < 0.05).Serum ZC3H13 concentration in gastric cancer group was significantly higher than that in healthy control group (P < 0.05).The expression level of ZC3H13 in gastric cancer tissues and peripheral blood was related to gender, differentiation degree, clinical stage and infiltration depth of gastric cancer (P < 0.05).Multivariate analysis showed that ZC3H13 expression was not an independent risk factor for poor prognosis of gastric cancer patients (P > 0.05).The AUC was 0.826(P < 0.05), indicating good diagnostic value.The critical value of serum ZC3H13 protein concentration was 4.87 ng/ml, and the sensitivity and specificity of ZC3H13 in the diagnosis of gastric cancer were 98.8% and 50.0%. Conclusion ZC3H13 is highly-expressed in gastric cancer tissues, and the concentration of ZC3H13 protein in peripheral blood is also significantly increased.ZC3H13 may play an important role in the occurrence and development of gastric cancer, and has certain clinical diagnostic value for gastric cancer.

Research Progress on Clinical Trials of Antitumor Drugs / 肿瘤防治研究

Conventional clinical trials of antitumor drugs are conducted at clinical sites. In contrast, without clinical sites or site-less, digital clinical trials can be performed online. Virtual clinical trials analyze the therapeutic response of virtual patients to digital drugs using artificial intelligence and may reduce the costs of trials. Precision oncology trials based on biomarkers can invite more people to join clinical trials and guide the optimal choice of therapeutics for cancer patients. Oncology clinical trials will enter the era of digital, virtual and precision medicine.

Nerves and Tumorigenesis / 肿瘤防治研究

Human nerves promote the initiation of a variety of solid tumor via regulating the stem cells, inducing angiogenesis, interacting immune system and modulating microbiota, and axonogenesis further drives the growth of early cancer. Nerves have emerged as an important component of the tumor microenvironment, and the control of nerves and neural signaling will be used as the novel treatment of human cancers. The article reviews the mechanisms of nerves promoting tumorigenesis.

Research Progress on Relation Between Neutrophil and Breast Cancer / 肿瘤防治研究

Inflammation is one of the ten major characteristics of tumor. Neutrophil, as the main indicator reflecting the body's inflammatory status, can not only promote the development of breast cancer, but also inhibit the development of breast cancer, and is closely related to the treatment and prognosis of breast cancer. This article systematically reviews the relation between neutrophil and breast cancer, and further understands the role, mechanism and clinical value of neutrophil in breast cancer, so as to provide new methods for the treatment and prognosis of breast cancer.

Mechanisms of microrobot in cancer therapy / 国际肿瘤学杂志

Microrobots (from several millimetres down to a few micrometres in all dimensions) are constructed of nanoscale or molecular components and include various types of magneto-aerotactic bacteria microrobots, nanomotors, biohybrid magnetite microrobots, DNA nanorobots, soft-bodied robots and soft matter. Microrobots may enable applications in cargo delivery, targeting cancer, cellular manipulation and killing cancer. Microrobots swarms exhibit a variety of intriguing collective behaviors, and will serve as a functional bio-microrobot system for cancer " subtle therapy" .

Adaptive therapy of human cancers: targeting cancer evolution / 国际肿瘤学杂志

Cancer develops as result of evolution and targeting cancer evolution may be a promising cancer therapeutics. Cancer adaptive therapy is defined as targeting cancer evolution through selective adaption and co-evolution. Adaptive therapy of human cancers provides new insight into the strategies for adaption and integration through reprogramming the functions of vessel, immune, metabolism, microbiota and circadian clock, and facilitating hosts and their cancers evolution as a unit.

Application of selective CDK4/6 inhibitors in solid cancers therapy / 国际肿瘤学杂志

Cyclin-dependent kinase (CDK) inhibitors have been approved for the treatment of ER +/HER2-advanced breast cancer,and preclinical study and clinical trials are under way for multiple solid cancers.CDK4/6 inhibitors have shown good efficacy for human solid cancers,and it's future development direction are biomarkers,drug resistance and combined therapy in the future.

Cancer cell cycle therapeutics / 中国肿瘤临床

The era of cancer cell-cycle therapeutics has come.Proteins that directly regulate cell cycle progression,such as cyclin-de-pendent kinases(CDKs),checkpoint kinases(CHKs),Aurora kinases,Polo-like kinases,and the WEE1 kinase,are the main targets of cell-cycle therapeutics.In addition to the regulation of G1-S-phase progression,cell-cycle therapeutics also trigger anti-tumor immunity, regulate metabolism,and control transcription reprogramming.Combinations of cell cycle therapeutics with hormone therapy,phos-phatidylinositol 3-kinase(PI3K)inhibitors,epidermal growth factor receptor(EGFR)inhibitors,and autophagy inhibitors provide new therapeutic strategies for cancer treatment.Cancer cell-cycle therapeutics constitute a novel strategy for precision oncology in the age of integrative genomics.This review basically summarizes the targets and mechanisms of cancer cell-cycle therapeutics.

Advances of next-generation immune checkpoint blockade / 国际肿瘤学杂志

Immune checkpoint blockades can induce long lasting responses but only in a fraction of patients owing to deficient of antibody as well as the neglect of immune suppressive cells.Next-generation immune checkpoint blockades,including FcγR-binding anti-programmed cell death-1 (PD-1)/PD ligand 1 (PD-L1) antibodies,co-inhibitors of immune checkpoint,small-molecule modulators and antibody-drugs conjugated with PD-1/PD-L1,will overcome the deficiencies of current anti-PD-1/PD-L1 antibodies and will become the direction of immunotherapy in the future.

Methods to improve the treatment of antitumor angiogenesis / 肿瘤

Abnormal vessel and function are hallmarks of cancer, and they contribute to cancer progression and migration. Angiogenesis has become an attractive target for drug therapy, and several regulatory and signaling molecules governing angiogenesis are of interest. Angiogenesis inhibitors, intending to block tumor's blood supply and provide survival benefits for cancer patients, may fuel tumor progression and treatment resistance. Actionable strategies to improve clinical efficacy of angiogenesis inhibitors include vascular mimicry regulation, tumor vessel normalization, seeking predictive factors, multi-targeted drugs development and combinational therapeutics. Moreover, strategies aiming at alleviating tumor hypoxia while improving perfusion may enhance the outcome of antiangiogenic therapy. Angiogenesis inhibitors offer an avenue for the development of cancer therapy.

Holistic therapy of advanced non-small cell lung / 国际肿瘤学杂志

Holistic therapy of cancer is helping to design more effective cancer therapies by combination individual properties (such as performance status,histological types and molecular types) and novel clinical results.Holistic therapy in oncology reflects individual,precision,whole course and real-time treatment strategy,and includes sequential,synchronizational,interval and metronomic therapy models.Holistic therapy in oncology would be help in selecting appropriate choices for patients and clinic doctors.

Holistic therapy of advanced non-small cell lung / 国际肿瘤学杂志

Holistic therapy of cancer is helping to design more effective cancer therapies by combination individual properties (such as performance status,histological types and molecular types) and novel clinical results.Holistic therapy in oncology reflects individual,precision,whole course and real-time treatment strategy,and includes sequential,synchronizational,interval and metronomic therapy models.Holistic therapy in oncology would be help in selecting appropriate choices for patients and clinic doctors.

Advances of therapeutic cancer vaccines / 国际肿瘤学杂志

Therapeutic cancer vaccines offer a novel avenue for the development of cancer immunothe rapy.Tumor antigens can induce T cell antitumor immune responses,but lack of tumor-specific antigens has hampered clinical efficacy.Vaccine types include peptide vaccines,dendritic cell vaccines and oncolytic virus vaccines.Personalizing tumor vaccines may provide a new immunotherapeutic strategy to treat cancer.

Dysbiosis of gut microbiota drives cancer development / 国际肿瘤学杂志

Numerous studies support the importance of gut microbiota as environment factors in the development of cancer.The mechanisms that gut microbiota drive certain cancers include impacting immunity,modulating inflammation,inducing DNA damage,producing cancer promoting metabolites and regulating signaling pathway.Microbiome-based therapies provide potential prospects for cancer treatment.

Precision chemotherapy for the treatment of cancers / 国际肿瘤学杂志

Precision chemotherapy is the prospective direction of cancer chemotherapy,which involves the selection of the effective chemotherapy regimens based on the chemotherapy-related genes.Chemotherapyrelated genes include DNA repair genes,drug metabolism enzymes,drug transporters,apoptosis-related genes and cancer-related genes.These genes can predict the response and toxicity of chemotherapy,and determine the clinical outcome.

Cancer and aging / 国际肿瘤学杂志

The similar mechanism of human cancer and aging means that cancer is the natural result of aging.Mitochondrial replacement, genome editing, telomere synthesis and immune editing can induce cancer cell senescence and resist human aging, which may breach a limit to human lifespan.

Tumorigenesis and human brain / 肿瘤

Classical theories of origin for cancer neglect the role of human brain in most cases. Mentality is the product of brain, and the brain promotes tumorigenesis by regulating nervous system, immunological function, endocrine system and energy metabolism. Psychology will provide the means to control the brain activity which highlights the future applications for treating human cancers.

A multicenter, randomized, controlled, phase Ⅲ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.</p><p><b>METHODS</b>According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.</p><p><b>RESULTS</b>The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).</p><p><b>CONCLUSIONS</b>In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.</p>