• anaplastic lympho
  • Echinoderm microtubule-associated protein-like 4 and the anaplastic lymphoma kinase (EML4-ALK) fusion genes were identified in a subset of NSCLCs in 2007 (Soda et al. (springeropen.com)
  • For example, a recent clinical trial at the Massachusetts General Hospital Cancer Center, which examined the efficacy of crizotinib, a targeted therapy for patients with tumors known to harbor rearrangements of the ALK (anaplastic lymphoma kinase) gene, showed that nearly 60 percent of patients responded positively to the therapy drug. (massgeneral.org)
  • Approximate percentage of patients with tumors known to harbor rearrangements of the ALK (anaplastic lymphoma kinase) gene who responded positively to crizotinib in a recent clinical trial at the Massachusetts General Hospital Cancer Center. (massgeneral.org)
  • 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. (wikipedia.org)
  • The translocation creates a fusion gene consisting of the ALK (anaplastic lymphoma kinase) gene and the nucleophosmin (NPM) gene: the 3' half of ALK, derived from chromosome 2 and coding for the catalytic domain, is fused to the 5' portion of NPM from chromosome 5. (wikipedia.org)
  • Ceritinib was approved by the FDA in April 2014 for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. (wikipedia.org)
  • Some of the most important kinases that have been shown to undergo rearrangement in human cancers include the anaplastic lymphoma kinase (ALK), ROS1 kinase, and the neurotrophic receptor tyrosine kinases (NTRKs). (wikipedia.org)
  • 2016
  • For a "Cancer Dialogue" held during the 2016 American Association of Cancer Research (AACR) Annual Meeting, half a dozen stellar participants from the resea. (ascopost.com)
  • Excitement was high on the last day of the 2016 Annual Meeting of the American Association for Cancer Research (AACR) in anticipation of Vice President Joseph R. Biden's remarks related to the Moonsho. (ascopost.com)
  • Interim results from two ongoing phase 1 trials have been reported at the 2016 AACR American Association for Cancer Research Conference in April 2016: among the patients treated with entrectinib, four patients had tumors harboring NTRK fusions, including patients with non-small cell lung cancer (NSCLC), mCRC, salivary gland cancer, and astrocytoma. (wikipedia.org)
  • targets
  • Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. (ox.ac.uk)
  • We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements. (ox.ac.uk)
  • On the basis of the documented effects on both local and systemic disease, it is widely perceived that combined modality therapy with suppression of the AR axis simultaneously enhances the cytotoxic effects of radiotherapy on the primary prostate cancer and also targets occult metastases. (aacrjournals.org)
  • Deletion lengthening at chromosomes 6q and 16q targets multiple tumor suppressor genes and is associated with an increasingly poor prognosis in prostate cancer. (nih.gov)
  • Gene rearrangements, leading to the expression of constitutively activated fusion tyrosine kinase receptors, have been increasingly identified as a common feature of malignancies over the last three decades, and success has been demonstrated using these rearrangements as targets for drug development. (wikipedia.org)
  • melanoma
  • However, it was detected in the majority of 57 prostate tumors analyze and has been reported in non-small cell lung cancers, melanoma and head and neck squamous cell cancers Along with chromothripsis, and break-fusion-bridge cycles, chromoplexy is an example of chromoanagenesis. (wikipedia.org)
  • These statistics are similar for other targeted therapies, including those used for EGFR-mutant lung cancers and other agents used in melanoma. (massgeneral.org)
  • Proteins
  • In recent years, treatment for genetically defined cancers-those cancers known to harbor specific genetic abnormalities-has moved away from general cytoxic chemotherapies toward agents that specifically target proteins and signaling pathways that cancer cells need for their growth. (massgeneral.org)
  • The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. (wikipedia.org)
  • Entrectinib (RXDX-101) is a selective tyrosine kinase inhibitor developed by Ignyta, Inc., with specificity, at low nanomolar concentrations, for all of three Trk proteins (encoded by the three NTRK genes, respectively) as well as the ROS1, and ALK receptor tyrosine kinases. (wikipedia.org)
  • Expression of the proteins encoded by these tyrosine kinase fusion genes can, in most cases, be shown to function independently as oncogenic drivers, capable of activating critical downstream pathways involved in the malignant phenotype, resulting in transformation of cells in vitro. (wikipedia.org)
  • The proteins made by both genes are essential for repairing damaged DNA (see Figure of recombinational repair steps). (wikipedia.org)
  • kinase
  • Other agents that have produced favorable response rates include inhibitors that target mutations in the BRAF, MEK (mitogen-activated protein kinase/Erk kinase), and EGFR (epidermal growth factor receptor) genes. (massgeneral.org)
  • ING1 is located near the following genes on Chromosome 13 CARKD Carbohydrate Kinase Domain-Containing Protein (Unknown Function) COL4A2: A2 Subunit of type IV collagen RAB20: Potential regulator of Connexin 43 trafficking. (wikipedia.org)
  • The expression of such gene fusions in a tumor can create a phenomenon termed 'oncogene addiction' in which the tumor becomes dependent on signaling by the aberrant kinase pathway, thus rendering its survival and continued proliferation exquisitely sensitive to targeted inhibition with small molecule tyrosine kinase inhibitor drugs. (wikipedia.org)
  • Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. (wikipedia.org)
  • The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor Retinoblastoma protein making CDK6 an important protein in cancer development. (wikipedia.org)
  • protein
  • The BRCA2 gene (MIM#600185) is a tumour suppressor gene that codes for a 3,418 amino-acid protein. (beds.ac.uk)
  • ING1 (Inhibitor Of Growth Family Member 1) is a Protein Coding gene. (genecards.org)
  • Inhibitor of growth protein 1 is a protein that in humans is encoded by the ING1 gene. (wikipedia.org)
  • The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. (wikipedia.org)
  • Zinc finger protein Rlf is a protein that in humans is encoded by the RLF gene. (wikipedia.org)
  • S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the S100A2 gene. (wikipedia.org)
  • Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9. (wikipedia.org)
  • Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL) located on chromosome 9. (wikipedia.org)
  • T-cell leukemia homeobox protein 3 is a protein that in humans is encoded by the TLX3 gene. (wikipedia.org)
  • BRCA2 and BRCA2 (/ˌbrækəˈtuː/) are a human gene and its protein product, respectively. (wikipedia.org)
  • The human reference BRCA 2 gene contains 27 exons, and the cDNA has 10,254 base pairs coding for a protein of 3418 amino acids. (wikipedia.org)
  • As a result of these mutations, the protein product of the BRCA2 gene is abnormal and does not function properly. (wikipedia.org)
  • Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene. (wikipedia.org)
  • It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. (wikipedia.org)
  • These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. (wikipedia.org)
  • Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. (wikipedia.org)
  • Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein-Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development. (wikipedia.org)
  • In cancer cells, EP300 mutations prevent the gene from producing any functional protein. (wikipedia.org)
  • BRCA2
  • Large rearrangements are less frequent in the BRCA2 gene than in BRCA1 . (beds.ac.uk)
  • Large BRCA2 rearrangements were analysed by QMPSF (Quantitative Multiplex PCR of Short Fluorescent Fragments) or MLPA (Multiplex Ligation-Dependent Probe Amplification). (beds.ac.uk)
  • The exon 3 deletion was characterized with a "zoom-in" dedicated CGH array to the BRCA2 gene and sequencing. (beds.ac.uk)
  • Large rearrangements of BRCA2 were detected in six index cases out of 2058 tested (3% of all deleterious BRCA2 mutations). (beds.ac.uk)
  • In contrast to the BRCA1 gene, reports of large rearrangements in the BRCA2 gene are rare. (beds.ac.uk)
  • In our two French Medical Centres (St Cloud and Strasbourg), a retrospective screening for large rearrangements in the BRCA2 gene on 2058 index cases that lacked BRCA1-2 point mutations, led to the identification of five out-of-frame large rearrangements. (beds.ac.uk)
  • Additionally, for the first time, a novel large rearrangement in the BRCA2 gene (Δ3 LR) that leads to a complete in frame deletion of exon 3 has been identified. (beds.ac.uk)
  • The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3). (wikipedia.org)
  • Methods to diagnose the likelihood of a patient with mutations in BRCA1 and BRCA2 getting cancer were covered by patents owned or controlled by Myriad Genetics. (wikipedia.org)
  • Although the structures of the BRCA1 and BRCA2 genes are very different, at least some functions are interrelated. (wikipedia.org)
  • Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development. (wikipedia.org)
  • Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause an increased risk of cancer. (wikipedia.org)
  • BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs in the gene. (wikipedia.org)
  • People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia. (wikipedia.org)
  • relapse
  • Despite their ability to induce dramatic tumor responses with fewer side effects, the effectiveness of targeted therapies is currently limited because the majority of patients using these agents develop resistance over time, resulting in a relapse or worsening of the cancer-the majority of patients will relapse within one year of starting therapy. (massgeneral.org)
  • For example, approximately half of patients with lung cancers that have the ALK gene rearrangement relapse within 10 months. (massgeneral.org)
  • clinical
  • As part of our mission to eliminate cancer, MD Anderson researchers conduct hundreds of clinical trials to test new treatments for both common and rare cancers. (mdanderson.org)
  • These data can also be used to help determine clinical trial eligibility for patients with alterations in genes not amenable to current FDA-approved targeted therapies. (mayomedicallaboratories.com)
  • Alterations in the expression of cytoskeletal regulatory genes and migration properties of BCP represent early events in the evolution of the disease, from the preleukemic phase to the clinical onset, and suggest new strategies for effective eradication of leukemia. (aacrjournals.org)
  • We assessed the association between ERG rearrangement status and clinical benefit from abiraterone acetate. (aacrjournals.org)
  • Hugh J. Jewett developed the first clinical staging of bladder cancer, created the basis for our modern-day staging of bladder cancer and developed a prognostic model that could be easily shared among physicians and patients. (jhu.edu)
  • To drive this work, researchers at the Cancer Center employ an integrated research strategy, beginning with preclinical models (e.g., tumor cell lines or tumors in genetically engineered rodent models) and detailed analysis of patient specimens, which then culminate in clinical trials. (massgeneral.org)
  • Carefully designed clinical trials demonstrate whether new strategies for predicting or preventing drug resistance improve the outcome of cancer therapy for patients. (massgeneral.org)
  • An open label, multicenter, global phase 2 clinical trial called STARTRK-2 is currently underway to test the drug in patients with ROS1/NTRK/ALK gene rearrangements. (wikipedia.org)
  • tumors
  • Its prevalence across cancers is not known, because only a few types of tumors have been analyzed for chromoplexy in the published literature. (wikipedia.org)
  • The preliminary results seen with entrectinib in the phase I studies of patients with NTRK/ROS1/ALK fusions have led to the initiation of an open-label, multicenter, global, phase II basket study to examine the use of entrectinib in patients having tumors with these gene rearrangements. (wikipedia.org)
  • It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. (wikipedia.org)
  • Studies suggest that EP300 mutations may also play a role in the development of some prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. (wikipedia.org)
  • novel
  • W illiam G. Kaelin, Jr, MD , Chair of the Executive Committee for Research at Dana-Farber Cancer Institute, received the 10th annual Princess Takamatsu Award for "novel and significant work" in cancer from the American Association for Cancer Research (AACR). (ascopost.com)
  • This rearrangement occurs early in the differentiation process and creates novel T-cell receptors that mimic the structure of normal antibodies but are not able to function properly. (wikipedia.org)
  • Clonal gene rearrangements create novel or new surface antibodies during early differentiation. (wikipedia.org)
  • Regulation
  • Among its related pathways are Chromatin Regulation / Acetylation and Senescence and Autophagy in Cancer . (genecards.org)
  • CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression in the point of regulation named R or restriction point. (wikipedia.org)
  • detect
  • A semi-automated PCR method involving fluorescent-labeled PCR products and non-denaturing capillary electrophoresis is performed to detect only complete TCRB rearrangements. (mdanderson.org)
  • The standard test used to detect this gene in tumor samples is fluorescence in situ hybridization (FISH) by a US FDA approved kit. (wikipedia.org)
  • citation needed] Other techniques like reverse-transcriptase PCR (RT-PCR) can also be used to detect lung cancers with an ALK gene fusion but not recommended. (wikipedia.org)
  • leukemia
  • The t(9;22) translocation results in the head-to-tail fusion of the BCR and ABL1 genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia. (wikipedia.org)
  • Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). (wikipedia.org)
  • This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. (wikipedia.org)
  • For example, researchers have found a translocation between chromosomes 8 and 22 in several people with a cancer of blood cells called acute myeloid leukemia (AML). (wikipedia.org)
  • alterations
  • Next-generation sequencing has recently emerged as an accurate, cost-effective method to identify alterations across numerous genes known to be associated with response or resistance to specific targeted therapies. (mayomedicallaboratories.com)