In real-time ultrasound,molecular targeted contrast agent is introduced into the blood circulation through peripheral intravenous injection to enhance the imaging signal of target lesions after binding to the corresponding intravascular receptors,which can realize early diagnosis,staging of diseases,assessment of treatment response,and targeted treatment.In addition,molecular targeted ultrasound contrast agents provide a platform for the delivery of drugs and genes via microbubbles,and nanoscale contrast agents can be infiltrated through vascular endothelium into the interstitial space of the lesion for imaging or treatment.The available studies of molecular targeted ultrasound contrast agents mainly focus on the preclinical trials.Some clinical trials have been conducted in humans and preliminarily confirm the safety and feasibility of targeted ultrasound contrast agents.The molecular targeted ultrasound contrast agents enjoy a broad prospect in clinical application.
Humans ; Contrast Media/chemistry* ; Molecular Targeted Therapy ; Ultrasonography/methods* ; Diagnostic Imaging

With the in-depth study of tumor immunity, immunotherapy represented by immune checkpoint inhibitors has made a great breakthrough in solid tumors. Small cell lung cancer (SCLC) accounts for about 15%-20% of all lung cancers, with high malignancy, early metastasis and lack of effective treatment strategy. The appearance of immune checkpoint inhibitors brings new hope for SCLC. Several clinical trials have demonstrated the persistent efficacy and clinical activity of the programmed death receptor/ligand 1 (PD-1/L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the treatment of SCLC. However, its efficacy and safety are not very accurate, and the markers that can effectively predict the efficacy of immunotherapy have not been concluded. In this paper, for further changing the treatment strategy of SCLC clinical practice and providing theoretical basis of research, we reviewed the progress of immune checkpoint inhibitors, related markers in the treatment of SCLC by exploring the value, problems and challenges of immunotherapy in SCLC.
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Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; immunology ; Molecular Targeted Therapy ; methods ; Prognosis ; Small Cell Lung Carcinoma ; diagnosis ; drug therapy ; immunology

“Precision” trials, using reasonably integrated biomarker targets and molecularly selective anticancer agents, have become a major concern for both patients and their physicians. As next-generation sequencing, which is a parallel analysis method, becomes quicker, easier, and more accurate, precision medicine-based approaches are becoming more generalized in determining treatments for cancer patients. However, it is not applicable to all cancer patients because of current high prices, limited reimbursement coverage, low prevalence of driver genetic mutations, and lack of treatable drugs. To solve these problems, the Republic of Korea has been operating the Cancer Precision Medicine Diagnosis and Treatment (K-MASTER) Enterprise since its establishment in June 2017. The aim of the project was to conduct large-scale genomic analyses, appropriate matching targeted clinical trials, and data management, which incorporates genomic and clinical information. In this review, we introduce the goals and composition of this project and describe the progress of the project to date.
Antineoplastic Agents ; Diagnosis ; High-Throughput Nucleotide Sequencing ; Humans ; Methods ; Molecular Targeted Therapy ; Precision Medicine ; Prevalence ; Republic of Korea

Radiomics handles imaging biomarker from high-throughput feature extraction through complex pattern recognition that is difficult for human to process. Recent medical paradigms are rapidly changing to personalized medicine, including molecular targeted therapy, immunotherapy, and theranostics, and the importance of biomarkers for these is growing day by day. Even though biopsy continues to gold standard for tumor assessment in personalized medicine, imaging is expected to complement biopsy because it allows whole tumor evaluation, whole body evaluation, and non-invasive and repetitive evaluation. Radiomics is known as a useful method to get imaging biomarkers related to intratumor heterogeneity in molecular targeted therapy as well as one-size-fits-all therapy. It is also expected to be useful in new paradigms such as immunotherapy and somatostatin receptor (SSTR) or prostate-specific membrane antigen (PSMA)-targeted theranostics. Radiomics research should move to multimodality (CT, MR, PET, etc.), multicenter, and prospective studies from current single modality, single institution, and retrospective studies. Image-quality harmonization, intertumor heterogeneity, and integrative analysis of information from different scales are thought to be important keywords in future radiomics research. It is clear that radiomics will play an important role in personalized medicine.
Biomarkers ; Biopsy ; Complement System Proteins ; Humans ; Immunotherapy ; Membranes ; Methods ; Molecular Targeted Therapy ; Population Characteristics ; Precision Medicine ; Prospective Studies ; Receptors, Somatostatin ; Retrospective Studies ; Theranostic Nanomedicine ; Weights and Measures

OBJECTIVE: To decipher the possible mechanisms of Sinomenium Acutum (SA) in treating diseases by a bioinformatics method. METHODS: SA ingredients were searched according to Chinese Pharmacopoeia, Chinese Medicine Dictionary and Traditional Chinese Medicines Database (TCMD). Active compounds and target proteins of SA were acquired through the Pubchem platform. Pathway, network and function analyses of SA were performed with ingenuity pathway analysis (IPA), a bioinformatics analysis platform. Disease, biofunction-target networks were established with Cytoscape. RESULTS: Eighteen ingredients from SA were obtained. Seven active ingredients with 31 active target proteins were acquired according to PubChem Bioassay test. By IPA analysis, 277 canonical pathways belonging to 17 function categories were collected, 23 kinds of diseases, 21 categories bio-functions were obtained. Based on P value, calculated by IPA, the top 5 significant pathway of SA targets include phosphatidylinositol 3 kinase/Akt (PI3K/Akt) signaling, prostate cancer signaling, macrophage migration inhibitory factor (MIF) regulation of innate immunity, Guanosine-binding protein coupled receptor (GPCR) signaling, and ataxia telangiectasia mutated protein (ATM) signaling. Disease and bio-function network analysis indicated that mitogen activated protein kinase 1 (MAPK1), MAPK3, p65 nuclear factor κB (RELA), nuclear factor of κB inhibitor alpha (NFκBIA), interleukin 1β(IL-1β), prostaglandin G/H synthase 2 (PTGS2) and tumor protein 53 (TP53) were the critical targets in various diseases treated by SA. CONCLUSION In the different view of target, pathway, disease and bio-function, inflammation was found to be a central theme in many chronic conditions. SA could be used not only as an anti-inflammatory agent, but also for the treatment of cancers, neurological diseases, psychological disorders and metabolic diseases.
Computational Biology ; methods ; Disease ; Humans ; Molecular Targeted Therapy ; Proteins ; metabolism ; Signal Transduction ; Sinomenium ; chemistry

The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for therapeutic interventions in various cancer types.
Animals ; Citric Acid Cycle ; drug effects ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Oncogenes ; genetics ; Tumor Suppressor Proteins ; metabolism

Cancer stem cells (CSCs), a subpopulation of tumor cells, have self-renewal and multi-lineage differentiation abilities that play an important role in cancer initiation, maintenance, and metastasis. An accumulation of evidence indicates that CSCs can cause conventional therapy failure and cancer recurrence because of their treatment resistance and self-regeneration characteristics. Therefore, approaches that specifically and efficiently eliminate CSCs to achieve a durable clinical response are urgently needed. Currently, treatments with chimeric antigen receptor-modified T (CART) cells have shown successful clinical outcomes in patients with hematologic malignancies, and their safety and feasibility in solid tumors was confirmed. In this review, we will discuss in detail the possibility that CART cells inhibit CSCs by specifically targeting their cell surface markers, which will ultimately improve the clinical response for patients with various types of cancer. A number of viewpoints were summarized to promote the application of CSC-targeted CART cells in clinical cancer treatment. This review covers the key aspects of CSC-targeted CART cells against cancers in accordance with the premise of the model, from bench to bedside and back to bench.
Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; immunology ; pathology ; therapy ; Neoplastic Stem Cells ; pathology ; Receptors, Chimeric Antigen ; metabolism ; T-Lymphocytes ; immunology ; metabolism ; Translational Medical Research

Aptamers are single-stranded DNA or RNA which are isolated from synthesized random oligonucleotide library in vitro via systematic evolution of ligands by exponential enrichment (SELEX) and can bind to metal ions, small molecules, carbohydrates, lipids, proteins, and others targets with high affinity and specificity. Aptamers have the advantages of simple preparation, good thermal stability, and low immunogenicity and have great potential in the medical fields such as molecular imaging, biosensing, early diagnosis of diseases, and targeted therapy. Aptamer technology may be useful for early diagnosis and targeted therapy of pediatric cancer, and may avoid the side effects of conventional chemotherapy, such as growth and development disorders and long-term organ dysfunction. This article reviews the latest research advances in the selection and application of aptamers for pediatric cancer.
Child ; Early Detection of Cancer ; Humans ; Molecular Targeted Therapy ; Neoplasms ; diagnosis ; drug therapy ; SELEX Aptamer Technique ; methods

In recent years, epidermal growth factor receptor tyrosine kinase inhibitors have been recommended by many guidelines as first-line drugs for advanced non-small cell lung cancer (NSCLC) with EGFR gene mutations and no resistance. However, with the prolongation of medication time, most appear acquired resistance. In recent years, breakthroughs in inhibitors of programmed death-1 (PD-1) and its ligand (PD1 ligand, PD-L1) have rapidly changed the therapeutic model of NSCLC. Recent studies have shown that the efficacy of immune checkpoint inhibitors in EGFR-mutant NSCLC patients is not satisfactory, which might be caused by low PD-L1 expression, inhibitory immune microenvironment and low tumor mutation load. This review will elaborate the immune microenvironment of NSCLC patients with EGFR mutation, the latest study progression of immune checkpoint inhibitors and its combined with TKI, expecting to bring new hopes for the treatment of EGFR-mutant NSCLC patients.
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Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; immunology ; ErbB Receptors ; genetics ; Humans ; Immune System ; drug effects ; immunology ; Lung Neoplasms ; drug therapy ; genetics ; immunology ; Molecular Targeted Therapy ; methods ; Mutation

Targeted therapy is one of the major treatment modalities in advanced non-small cell lung cancer (NSCLC) with sensitive driver gene mutations. BRAF is considered a promising oncogenic driver in NSCLC after the discovery of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion and ROS1 rearrangement. BRAF V600E mutation accounts for more than half of BRAF mutations, which is a potential therapeutic target for advanced NSCLC. This review aims to summarize the advancements of BRAF gene mutation and targeted therapy for BRAF mutation in NSCLC.
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Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; pathology ; Drug Resistance, Neoplasm ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Molecular Targeted Therapy ; methods ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics