• 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)
  • Such matchmaking is changing the way trials unfold, as illustrated by the story of crizotinib, a drug that inhibits several proteins thought important for cancer growth, including a protein called anaplastic lymphoma kinase (ALK). (dana-farber.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)
  • tumors
  • This phenomenon was first identified in prostate cancer by whole genome sequencing of prostate tumors. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • These proteins are expressed and non-infectious particles are released in various cells, particularly in tumors and cancer cell lines derived from teratocarcinomas and melanomas ( 5 - 7 ). (frontiersin.org)
  • Shortly after, several lung cancer patients with ALK rearrangements in their tumors enrolled. (dana-farber.org)
  • EML4-ALK-rearrangement in NSCLC is exclusive and not found in EGFR- or KRAS-mutated tumors. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • prostate cancer
  • Molecular subtyping of primary prostate cancer reveals specific and shared target genes of different ETS rearrangements. (ox.ac.uk)
  • Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. (aacrjournals.org)
  • In this issue of Clinical Cancer Research , Hedayati and colleagues ( 1 ) report a novel, but possibly counterintuitive, strategy of exploiting sequential androgen suppression and stimulation to increasingly sensitize prostate cancer cells to radiotherapy. (aacrjournals.org)
  • The combination of androgen suppression and radiotherapy is a time-honored treatment regime with proven efficacy of advancing cure rates in patients with high-risk and locally advanced prostate cancer. (aacrjournals.org)
  • Interplay between androgen receptor (AR) axis manipulation and DNA repair in prostate cancer. (aacrjournals.org)
  • Given the positive-feedback circuit linking AR axis stimulation and DNA repair, it would suggest, in principle, that targeting the AR axis represents a very sound and attractive strategy for potentiating the DNA-damaging effects of cytotoxic therapies in prostate cancer. (aacrjournals.org)
  • Abiraterone acetate improves survival in metastatic castration-resistant prostate cancer (mCRPC), but not all patients respond. (aacrjournals.org)
  • In prostate cancer, chromoplexy may cause multiple oncogenic events within a single cell cycle, providing a proliferative advantage to a (pre-)cancerous cell. (wikipedia.org)
  • In at least some instances of prostate cancer, chromoplexy can occur in multiple subsequent rounds. (wikipedia.org)
  • Punctuated evolution of prostate cancer genomes. (wikipedia.org)
  • The genomic complexity of primary human prostate cancer. (wikipedia.org)
  • Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. (wikipedia.org)
  • Screening for breast and prostate cancer based on genetic risk factors as well as age could reduce the number of people screened without a significant reduction in the number of cancers detected, a new study suggests. (bionews.org.uk)
  • They compared current screening approaches for breast and prostate cancer with the new model and found using the new model would have resulted in 24 percent (%) fewer women being screened and 14% fewer cases of breast cancer being detected. (bionews.org.uk)
  • They also found 16% fewer men would be eligible for prostate cancer screening but only 3% fewer cases would be detected. (bionews.org.uk)
  • Prostate cancer is the most common cancer in men and 37,000 men are diagnosed each year in the UK. (bionews.org.uk)
  • A DNA test for men with prostate cancer could indicate whether their cancer is likely to recur after treatment, and if so, how aggressively, say researchers from the University of Pittsburg School of Medicine, USA. (bionews.org.uk)
  • Sequencing tissue samples from patients with deadly forms of prostate cancer has revealed previously undefined, drug-resistant tumour types that are ten times more mutated than other varieties, report researchers. (bionews.org.uk)
  • Genomes of early onset prostate cancer. (embl.de)
  • Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients. (embl.de)
  • 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)
  • Lymphoma
  • The new Blood Cancer Research Partnership formed by Dana-Farber, the Lymphoma and Leukemia Society (LLS), and the LLS Therapy Acceleration Program is taking aim at another constraint: proximity. (dana-farber.org)
  • Interestingly, the histiocytic tumor component has been shown to harbor BCL2 gene translocations that are identical to those found in the lymphoma. (stanford.edu)
  • We present one case of histiocytic sarcoma and initially occult follicular lymphoma in which detection of a BCL2 gene translocation helped support the diagnosis. (stanford.edu)
  • We also provide follow up regarding a previously published case of histiocytic sarcoma with IGH/BCL2 fusion gene in which the patient subsequently developed follicular lymphoma and, later, diffuse large B-cell lymphoma. (stanford.edu)
  • Lutzner cells can form cutaneous T-cell lymphoma, which is a form of skin cancer. (wikipedia.org)
  • kinase
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Mutation
  • Results from genetic tests done on his tumor revealed a mutation in the ALK gene that qualified Perry, an active 23-year-old, for a clinical trial of an experimental targeted drug. (dana-farber.org)
  • This mutation is a clonal gene rearrangement at the TCR-γ gene. (wikipedia.org)
  • If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. (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)
  • neoadjuvant
  • In a meta-analysis of neoadjuvant studies totaling over 18,000 patients, achievement of pathologic complete response was associated with significantly reduced disease recurrence and mortality across the various breast cancer subtypes. (ascopost.com)
  • 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)
  • Called targeted therapies, these agents can induce dramatic clinical responses and offer significant therapeutic benefits in treating many previously hard-to-treat cancers, including certain melanomas, colorectal cancers, thyroid cancers, and advanced lung cancers. (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)
  • As more of these targeted drugs enter clinical testing, more phase 1 trials are recruiting patients based on the tumor's genetic profile, regardless of the type of cancer. (dana-farber.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)
  • Squamous
  • Familial cases of neuroblastoma Inflammatory myofibroblastic tumor Adult and pediatric renal cell carcinomas Esophageal squamous cell carcinoma Breast cancer, notably the inflammatory subtype Colonic adenocarcinoma Glioblastoma multiforme Anaplastic thyroid cancer Xalkori (crizotinib), produced by Pfizer, was approved by the FDA for treatment of late stage lung cancer on August 26, 2011. (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)
  • Entrectinib
  • Entrectinib definition Ignyta Receives Orphan Drug Designation From FDA For Entrectinib For The Treatment Of Molecularly Defined Subsets Of Non-Small Cell Lung Cancer Ignyta's entrectinib an Orphan Drug in Europe for neuroblastoma Puig de la Bellacasa, R (2 April 2013). (wikipedia.org)
  • differentiation
  • 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)
  • 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)
  • It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. (wikipedia.org)
  • regulates
  • Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development. (wikipedia.org)
  • Oncology
  • You want to open up trials that can move the field forward," says Ursula Matulonis, MD , medical director of Gynecologic Oncology in the Susan F. Smith Center for Women's Cancers at Dana-Farber. (dana-farber.org)
  • leukemia
  • T-cell leukemia homeobox protein 3 is a protein that in humans is encoded by the TLX3 gene. (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)
  • human
  • With more than 500,000 elements, there are over 20-fold more HERV sequences than there are human genes. (frontiersin.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)
  • EP300 is closely related to another gene, CREB binding protein, which is found on human chromosome 16. (wikipedia.org)
  • amino
  • The first 140 amino acids of the TMEM106A protein, including portions of DUF1356 and a transmembrane region, are deleted along with BRCA1 during early-onset breast cancer. (wikipedia.org)
  • BRCA1
  • It is located at 17q21.31 on the plus strand next to cancer-related genes NBR1 and BRCA1. (wikipedia.org)
  • Although the structures of the BRCA1 and BRCA2 genes are very different, at least some functions are interrelated. (wikipedia.org)
  • Patients
  • Your gift will help support our mission to end cancer and make a difference in the lives of our patients. (mdanderson.org)
  • The ALK rearrangements that are found in up to 5 % of patients with NSCLC are related to younger age, no history of smoking and distinct clinicopathological features such as adenocarcinoma histology (Shaw et al. (springeropen.com)
  • However, our data suggest that 2+ Edel cancers, accounting for 15% of all mCRPC patients and previously associated with a worse outcome, derived the greatest benefit. (aacrjournals.org)
  • Trials exist for patients of all stages, from those with stage I cancer, the earliest detectable cancer, to those with stage IV cancer, the most advanced disease. (dana-farber.org)
  • In a smaller fraction of ALCL patients, the 3' half of ALK is fused to the 5' sequence of TPM3 gene, encoding for tropomyosin 3. (wikipedia.org)
  • citation needed] ALK lung cancers are found in patients of all ages, although on average these patients tend to be younger. (wikipedia.org)
  • ALK lung cancers are more common in light cigarette smokers or nonsmokers, but a significant number of patients with this disease are current or former cigarette smokers. (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)
  • breast cancer
  • For our model to be used women would need to have a genetic test before the age of 35', said Dr Pashayan, explaining how the approach would work in breast cancer screening. (bionews.org.uk)
  • Breast cancer is the most commonly diagnosed cancer in the UK. (bionews.org.uk)
  • The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (breast cancer 2) are maintained by the HGNC. (wikipedia.org)
  • Certain variations of the BRCA2 gene increase risks for breast cancer as part of a hereditary breast-ovarian cancer syndrome. (wikipedia.org)