|
Crizotinib
Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). It acts as an ALK ( anaplastic lymphoma kinase) and ROS1 ( c-ros oncogene 1) inhibitor. Medical uses Crizotinib is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) or relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. It is also indicated for the treatment of unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors (IMT). Mechanism of action Crizotinib has an aminopyridine structure, and functions as a protein kinase inhibitor by competitive binding within the ATP-binding pocket of target kinases. About 4% of patients with non-small cell lung carcinoma have a chromosomal rearrangement that generates a fusion gene between '' EML4'' ('echinoderm microtubule-associated protein-like 4') and ''A ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
C-ros Oncogene 1
Proto-oncogene tyrosine-protein kinase ROS is an enzyme that in humans is encoded by the ''ROS1'' gene. Function This proto-oncogene, highly expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. Role in cancer ''ROS1'' is a receptor tyrosine kinase (encoded by the gene ''ROS1'') with structural similarity to the anaplastic lymphoma kinase (ALK) protein; it is encoded by the ''c-ros'' oncogene and was first identified in 1986. The exact role of the ''ROS1'' protein in normal development, as well as its normal physiologic ligand, have not been defined. Nonetheless, as gene rearrangement events involving ''ROS1'' have been described in lung and other cancers, and since such tumors have been found to be remarkably responsive to small mol ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Non-small Cell Lung Carcinoma
Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively (neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy). Types The most common types of NSCLC are squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma, but several other types occur less frequently. A few of the less common types are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. All types can occur in unusual histologic variants and as mixed cell-type combinations. Nonsquamous-cell carcinoma almost occupies the half of NSCLC. In the tissue classification, the central type contains about one-ninth. S ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anaplastic Lymphoma Kinase
Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ''ALK'' gene. Identification Anaplastic lymphoma kinase (ALK) was originally discovered in 1994 in anaplastic large-cell lymphoma (ALCL) cells. ALCL is caused by a (2;5)(p23:q35) chromosomal translocation that generates the fusion protein NPM-ALK, in which the kinase domain of ALK is fused to the amino-terminal part of the nucleophosmin (NPM) protein. Dimerization of NPM constitutively activates the ALK kinase domain. The full-length protein ALK was identified in 1997 by two groups. The deduced amino acid sequences revealed that ALK was a novel receptor tyrosine kinase (RTK), having an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. While the tyrosine kinase domain of human ALK shares a high degree of similarity with that of the insulin receptor, its ext ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anaplastic Lymphoma Kinase
Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ''ALK'' gene. Identification Anaplastic lymphoma kinase (ALK) was originally discovered in 1994 in anaplastic large-cell lymphoma (ALCL) cells. ALCL is caused by a (2;5)(p23:q35) chromosomal translocation that generates the fusion protein NPM-ALK, in which the kinase domain of ALK is fused to the amino-terminal part of the nucleophosmin (NPM) protein. Dimerization of NPM constitutively activates the ALK kinase domain. The full-length protein ALK was identified in 1997 by two groups. The deduced amino acid sequences revealed that ALK was a novel receptor tyrosine kinase (RTK), having an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. While the tyrosine kinase domain of human ALK shares a high degree of similarity with that of the insulin receptor, its ext ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hepatocyte Growth Factor Receptor
c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the ''MET'' gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor. MET is a single pass tyrosine kinase receptor essential for embryonic development, organogenesis and wound healing. Hepatocyte growth factor/Scatter Factor (HGF/SF) and its splicing isoform (NK1, NK2) are the only known ligands of the MET receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF/SF is restricted to cells of mesenchymal origin. When HGF/SF binds its cognate receptor MET it induces its dimerization through a not yet completely understood mechanism leading to its activation. Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
C-Met
c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the ''MET'' gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor. MET is a single pass tyrosine kinase receptor essential for embryonic development, organogenesis and wound healing. Hepatocyte growth factor/Scatter Factor (HGF/SF) and its splicing isoform (NK1, NK2) are the only known ligands of the MET receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF/SF is restricted to cells of mesenchymal origin. When HGF/SF binds its cognate receptor MET it induces its dimerization through a not yet completely understood mechanism leading to its activation. Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
K-Ras
''KRAS'' (Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide ( proliferate) or to mature and take on specialized functions ( differentiate). It is called ''KRAS'' because it was first identified as a viral oncogene in the Kirsten RAt Sarcoma virus. The oncogene identified was derived from a cellular genome, so , when found in a cellular genome, is called a proto-oncogene. The K-Ras protein is a GTPase, a class of enzymes which convert the nucleotide guanosine triphosphate (GTP) into guanosine diphosphate (GDP). In this way the K-Ras protein acts like a switch that is turned on and off by the GTP and GDP molecules. To transmit signals, it must be turned on by attaching (binding) to a molecule of GTP. The K-Ras protein is turned off (inactivated) when it converts the GTP to GDP. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Malignant
Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not self-limited in its growth, is capable of invading into adjacent tissues, and may be capable of spreading to distant tissues. A benign tumor has none of those properties. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis. Malignant tumors are also characterized by genome instability, so that cancers, as assessed by whole genome sequencing, frequently have between 10,000 and 100,000 mutations in their entire genomes. Cancers usually show tumour heterogeneity, containing multiple subclones. They also frequently have reduced expression of DNA repair enzymes due to epigenetic methylation of DNA repair genes or altered microRNAs that control DNA repair gene expression. Tumours can be detected through the visual ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological properties, its behavior, and the products of behavior. An organism's phenotype results from two basic factors: the expression of an organism's genetic code, or its genotype, and the influence of environmental factors. Both factors may interact, further affecting phenotype. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and then again in his 1982 book '' The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epidermal Growth Factor Receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer. Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Cohen shared the 1986 Nobel Prize in Medicine with Rita Levi-Montalcini for their discovery of growth factors. Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as Alzheimer's, while over-expression is associated with the development of a wide variety of tumors. Interruption of EGFR signalling, either ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
