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

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

“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

Squamous cell lung cancer (SqCLC) is a unique clinical and histologic category of non-small cell lung cancer (NSCLC). Most of patients with SqCLC tend to be older, typically at advanced stage, associated with smoking and have more complications. With progress of targeted therapy of lung cancer, we identified several potential actionable genetic abnormalities such as FGFR. Several FGFR inhibitors have been approved for clinical use in different cancers. And some of these agents are currently under investigation in clinical trials for SqCLC. This article summarizes the current knowledge about FGFR aberrations, the relative inhibitors in development and clinical data in SqCLC.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Molecular Targeted Therapy ; methods ; Mutation ; Receptors, Fibroblast Growth Factor ; genetics ; metabolism

Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.
Animals ; Biomarkers, Tumor ; metabolism ; Drug Resistance, Neoplasm ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; drug therapy ; metabolism ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; metabolism

With high morbidity and mortality, lung cancer is a major threat to human health and one of the focuses of tumor researches. Lung cancer stem cells (LCSCs) are regarded as a subpopulation of cells within lung cancer tissues with the capacity of self-renewal and differentiation, and might be related to tumorigenesis and heterogeneity of lung cancer. Tumor recurrence, metastasis and drug resistance of lung cancers could be clarified by LCSC hypothesis. Thus it's therapeutically prospective to target at these cells. This review summarizes the biomarkers of LCSCs and their aberrant signal pathways, as well as the therapeutic strategies targeting at LCSCs.
Animals ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Molecular Targeted Therapy ; methods ; Neoplastic Stem Cells ; drug effects ; pathology ; Signal Transduction ; drug effects

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit.We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.
Antineoplastic Agents ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Humans ; Medication Therapy Management ; Molecular Targeted Therapy ; adverse effects ; methods ; Neoplasms ; drug therapy ; genetics ; Pharmacogenomic Testing ; Therapies, Investigational ; 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