E1A: an adenovirus protein. E1A is an oncoprotein that affects cellular functions indirectly when they bind to and sequester cellular proteins, thereby preventing them from taking part in cellular processes. Some key cellular proteins E1A have been documented to interact with include Rb, cyclins, and cyclin-dependent kinases.
E2F1: regulator of S-phasespecific genes required for cell-cycle progression. The acetylation of E2F has positive effects on its DNA-binding functions, thereby stimulating transcription. When complexed with Rb, it acts as a transcriptional repressor.
Eastern Cooperative Oncology Group performance status: criteria used by doctors and researchers to define the progression of a patients disease, assessing how the disease affects daily living habits, and to assist in the determination of the appropriate treatment and prognosis.
EBNA1: the viral protein expressed during latent phases (I, II, and III) of Epstein-Barr virus (EBV) infection. EBNA1 is a DNA-binding protein that is required for the replication and maintenance of the episomal EBV genome. See Epstein-Barr virus (EBV).
E-cadherin: a calcium-dependent cell adhesion molecule that belongs to a family of developmental proteins responsible for maintaining structural integrity in tissues.
Ederer II method: a method that calculates the expected survival rates for patients under observation at each point of follow-up so the matched individuals are considered to be at risk until the corresponding patient with cancer dies or is censored (Cho H, et al: National Cancer Institute Technical Report 2011-01. http://surveillance.cancer.gov/reports/tech2011.01.pdf).
EEF2: gene coding for the eukaryotic translation elongation factor 2, which is responsible for translational elongation by translocation of the peptidyl-tRNA from the A site to the P site on the ribosome.
EEF2: a eukaryotic elongation factor that regulates the elongation phase of the translational process by translocating the growing mRNA from the ribosomal A site to the ribosomal P site. In mechanisms yet to be elucidated, mammalian target of rapamycin signaling regulates EEF2 activity. Phosphorylation of EEF2 (which occurs during nutrient starvation) is accompanied by a decrease in elongation rates, whereas dephosphorylation of EEF2 (which occurs in the presence of nutrients) is accompanied by increases in elongation rates.
effect size: in statistical inference, a measure of the strength of the relationship between two variables. When reporting statistical significance for an inferential test, effect size provides useful additional information. An inferential test may be statistically significant (ie, unlikely to have occurred by chance), but this does not necessarily mean the observed effect was large.
EGFRvIII: a mutant form of the epidermal growth factor receptor containing a deletion of exons 2 to 7 in the extracellular portion of the epidermal growth factor receptor. The kinase encoded by this mutant is constitutively active (ligand-independent) and highly transforming. It has been reported in about 40% of high-grade gliomas.
EIAC (enzyme-induced anticonvulsant agents): anticonvulsant agents (such as phenobarbital, phenytoin, and carbamazepine) that induce enzymes of the cytochrome P450 system, involved in drug metabolism.
eIF2: a eukaryotic translation initiation factor that forms a heterotrimeric complex with Met-tRNAiMet and GTP that is delivered to the 40S ribosome primed by eIF3, resulting in a 43S preinitiation complex ready to interact with capped mRNA.
eIF3: a eukaryotic translation initiation factor that binds to the 40S subunit of the ribosome, impeding its association with the 60S subunit. This primes the complex for the delivery of Met-tRNAiMet to the ribosome, setting the stage for initiation of translation.
eIF3κ: gene coding for the k subunit of eukaryotic translation initiation factor 3. See eIF3.
eIF4: also called eIF4F. eIF4 is a complex of eIF4A, eIF4E, and eIF4-γ. These eukaryotic translation initiation factors collectively recruit capped mRNA to the ribosome for translation. The eIF4F complex is involved in unwinding the secondary structure of mRNA during the process of translation initiation. eIF4E is a cap-binding protein. eIF4A possesses ATP-dependent RNA helicase activity and RNA-dependent ATPase activity. eIF4B is an RNA-binding protein that greatly enhances the activity of eIF4A. eIF4-γ is a protein of unknown function.
eIF4A: a protein with an RNA helicase activity and part of the translation complex with eIF4E.
eIF-4B: shows an RNA helicase activity, along with eIF-4F.
eIF4E (eukaryotic translation initiation factor 4E): a component of the translation initiation factor 4F (eIF4F) complex. eIF4E interacts directly with the cap structure of the mRNA. The interaction of eIF4E with eIF4E-binding proteins prevents the formation of eIF4F.
eIF-4G: a scaffold protein that interacts with eIF4E and allows the binding of eIF4A, eIF3 and the poly(A)-binding protein to form the translation complex.
EKI-785: tyrosine kinase inhibitor targeted against the tyrosine kinase activity of the epidermal growth factor receptor.
ELISA (enzyme-linked immunosorbent assay): assay used to detect the presence of an antibody or an antigen in a sample.
ELISpot: enzyme-linked immunospot that is exquisitely sensitive to assay minute amounts of mediators that are produced by cells. Typically, cells are deposited on a membrane coated with an antibody specific for a given protein. The protein of interest is captured directly around the secreting cell and is detected with an antibody specific for a different epitope. Coupled with colorimetry, the cells are visualized by specialized plate readers. Thus, the molecule is assayed before it is diluted in the supernatant, captured by receptors of adjacent cells, or degraded.
EMD 72000: a humanized monoclonal antibody targeted against the epidermal growth factor receptor (EGFR). EMD 72000 competitively inhibits growth-factor binding to EGFR, thereby inhibiting ligand-mediated activation of EGFR.
endometrial intraepithelial neoplasia EIN: a premalignant lesion of the endometrium composed of a localized monoclonal population of genetically altered glands. The presence of EIN on biopsy indicates a 30% chance of concurrent type I (endometrioid) endometrial cancer and a 45-fold increased risk for developing cancer in the next 20 years.
endoscopic ultrasound (EUS): a procedure in which a probe is inserted into the lumen of the GI tract and high-frequency sound waves (ultrasound waves) are generated to produce an image.
energy balance: the state at which the number of calories eaten equals the number of calories used. Energy balance is affected by physical activity, body size, amount of body fat and muscle, and genetics. Over time, excess energy balance (ie, greater energy intake compared with energy expenditure) can lead to obesity and numerous metabolic consequences, including hyperinsulinemia.
enrichment biomarkers: biomarkers that have strong scientific rationale and preclinical evidence for antitumor response but have yet to be clinically qualified.
enrichment trial: type of trial designed to enroll a group of patients believed to have a higher likelihood of response or lower
likelihood of toxicity on the basis of a tumor or host biomarker. An example of an enrichment trial would be enrolling patients with breast cancer onto a trial of the anti-HER2 monoclonal antibody
trastuzumab only if the tumor tissue overexpressed HER2.
enzyme-linked immunosorbent assay (ELISA): a sensitive, quantitative immunochemical test that involves an enzyme linked to an antibody or antigen to allow detection of a specific protein. Generally, the specimen is added to a surface, on which are immobilized
antibodies specific to the protein of interest. If the protein is present, it
will bind to the attached antibody layer. The presence of the bound protein
is then verified with antibodies that have been tagged with an enzyme, which causes the specimen to change color corresponding to the concentration of the target protein.
epidermal growth factor (EGF): the ligand for the epidermal growth factor receptor. See epidermal growth factor receptor (EGFR).
epidermal growth factor receptor 2 (EGFR2): See HER2/neu (human epidermal growth factor receptor 2).
epidermal growth factor receptor (EGFR): a member of a family of receptors (HER2, HER3, HER4 are other members of the family) that binds to the EGF, TGF-α, and other related proteins, leading to the generation of proliferative and survival signals within the cell. EGFR (also known as HER1) also belongs to the larger family of tyrosine kinase receptors and is generally overexpressed in several solid tumors of epithelial origin.
epidermal growth factor receptor tyrosine kinase inhibitor: inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor. See tyrosine kinase inhibitors.
epigenetic: the transfer of information from one cell to its descendants without the information being encoded in the nucleotide sequence of the DNA. The methylation of the promoter to inactivate a gene is an example of an epigenetic change. Epigenetic inheritance is typically transmitted in dividing cells. Although rare, it is occasionally seen in traits being transmitted from one generation to another. Epigenetic variants can arise spontaneously and just as spontaneously revert.
epigenome: the overall epigenetic state of a cell.
episome: a genetic particle of certain cells (ie, bacteria) that can exist on their own in the cytoplasm or as part of a chromosome. A plasmid is an example of an episome.
epithelial to mesenchymal transition (EMT): cellular changes that occur in epithelial cells to loss epithelial cell junction proteins and to gain mesenchymal phenotypes by expressing proteins such as vimentin and fibronectin.
epitope: region within an antigen that has the potential to give rise to an antibody response. With respect to protein antigens, epitopes may be defined on the basis of primary, secondary, or tertiary structure of the molecule and, consequently, maybe exposed or hidden within the molecule.
epitope spreading: the spreading of an adaptive immune
response to multiple antigens beyond the initial antigen recognized by the immune system. Epitope spreading has been described for both T-cell and B-cell responses.
EPO (erythropoietin): a glycoprotein hormone produced in the kidney and is responsible for the regulation of red blood cell production. By binding to EPO receptors on erythroid progenitor cells, EPO is responsible for progenitors maturing to functional erythrocytes. Recombinant EPO is therapeutically administered to patients who develop anemia.
EPOR (erythropoietin receptor): a receptor found on the surface of erythroid progenitor cells in the bone marrow that when bound with erythropoietin, stimulates erythroid progenitor cells to transform into erythrocytes.
epothilone B: a new drug, belonging to the class of drugs known as epothilones, which share a mechanism of action similar to taxanes. Epothilone B is a microtubule-stabilizing agent that is effective in tumor models that are resistant to taxanes.
Epstein-Barr virus (EBV): virus belonging to the herpes family of viruses. EBV is also called human herpes virus 4 and is an oncogenic virus that is responsible for B-cell transformation. It is associated with Hodgkin lymphoma, immunoblastic B-cell lymphomas, Burkitt's lymphoma, and nasopharyngeal carcinoma.
Epstein-Barr virus–encoded RNA (EBER): small nonpolyadenylated noncoding RNAs that are abundant viral products in latently infected cells.
ErbB: also called the human epidermal growth factor receptor (HER). ErbB belongs to the epidermal growth factor receptor (EGFR) family. ErbB1 (EGFR/HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4) are the four members that comprise this receptor family. See HER2⁄neu (human epidermal growth factor receptor 2).
ErbB1: see ErbB.
ErbB2: see ErbB.
ErbB3: see ErbB.
ErbB4: see ErbB.
ERCC1: excision repair cross-complementing gene, which encodes a nucleotide excision repair protein that repairs a range of lesions, including ultraviolet-induced thymine dimers and other photoproducts and also lesions caused by a variety of chemical agents.
ERG (ETS-related gene): gene located on chromosome 21q22 that encodes a transforming proto-oncogene that is expressed in hematopoietic progenitor and endothelial cells. In addition, ERG is expressed in early thymocytes and becomes downregulated as cells develop toward the T-cell lineage. ERG and other members of the ETS family are downstream effectors of mitogenic signaling transduction pathways and are involved in key steps regulating cell proliferation, differentiation, and apoptosis. ERG is also overexpressed in prostate cancer through gene fusions involving androgen-regulated promoters, most commonly TMPRSS2 and SLC45A3.
ERK (extracellular receptor kinase): a second messenger kinase (an enzyme adding phosphate groups from ATP). ERK belongs to the MAPK family and is responsible for transmitting signals from the cellular surface to the nucleus by the activation of transcription factors, including NF-κB. It belongs to the proliferative/mitogenic signal transduction pathway activated by tyrosine kinase receptors.
ERK/MAP kinase pathway: survival and proliferative pathways that channel signals through the activation of ERK and MAPK. See ERK (extracellular receptor kinase) and MAPK (mitogen-activated protein kinase).
ERK1: a member of the ERK family of protein kinases. See ERK (extracellular receptor kinase).
ERK1/ERK2 MAPK signaling pathway: see ERK/MAP kinase pathway.
ERK2: a member of the ERK family of protein kinases. See ERK (extracellular receptor kinase).
erlotinib: also known as Tarceva (Genentech, South San Francisco, CA). Erlotinib is a small molecule that inhibits the tyrosine kinase activity of epidermal growth factor receptor/HER1 and has been evaluated extensively in clinical trials in patients with non–small-cell lung cancer, pancreatic cancer, and glioblastoma multiforme.
erythropoietin: a glycoprotein hormone produced in the kidney, responsible for the regulation of RBC production. By binding to erythropoietin receptors on erythroid progenitor cells, it is responsible for progenitors maturing to functional erythrocytes. Recombinant erythropoietin is therapeutically administered to patients who develop anemia.
EST (expressed sequence tag) clones: a portion of cDNA that has been sequenced from one or both ends of the DNA. The human genome project allows for the generation of thousands of EST clones that may be ordered from the Integrated Molecular Analysis of Genome Expression consortium to be used in gene expression profiling using cDNA technology.
estrogen receptor (ER): ligand-activated nuclear proteins, belonging to the class of nuclear receptors, present in many breast cancer cells that are important in the progression of hormone-dependent cancers. After binding, the receptor-ligand complex activates gene transcription. There are two types of estrogen receptors (ERα and ERβ). ERα is one of the most important proteins controlling breast cancer function. ERβ is present in much lower levels in breast cancer, and its function is uncertain. Estrogen receptor status guides therapeutic decisions in breast cancer.
estrogen response element: specific DNA sequences with high affinity for the estrogen receptor that are involved in gene expression in response to estradiol.
ethidium bromide: a compound that binds to DNA and is visible under ultraviolet light. It is used to stain different DNA fragments dissolved in an agarose gel.
ETO (eight twenty-one): also called MTG8, the gene codes for a transcriptional co-repressor.
ETS transcription factors: family of transcription factors, characterized by an evolutionarily conserved DNA-binding domain, regulates expression of more than 300
target genes by binding to a purine-rich GGAA/T core sequence. At present, nearly 30 mammalian family members have been isolated. ETS signal transduction is implicated in hematopoiesis and angiogenesis at the earliest stages of embryogenesis and is later involved in tissue development. Deregulated
expression and/or formation of chimeric fusion proteins of the ETS family resulting from proviral insertion or chromosome translocation is associated with leukemias and with specific types
of solid tumors.
event-free survival: calculated from the date of diagnosis to the date of the first event, which is resistance, relapse, death, or second malignant neoplasm.
everolimus: see RAD001.
excess absolute risk (EAR): the excess number of outcomes observed (O) compared with the expected number of outcomes (E) based on patient characteristics (sex, age, etc): EAR = O-E.
exome: part of the genome formed by genes that code for proteins and other functional gene products (known as exons).
exon: segment of a gene that consists of a sequence of nucleotides that encodes amino acids in the protein. Genes are often
made up of multiple exons separated by introns that do not encode amino acids in the protein.
exon deletion: the deletion of a segment of a gene that consists of a sequence of nucleotides that encodes amino acids in the protein.
exploratory Investigational New Drug: guidance was developed by the US Food and Drug Administration to provide new regulatory pathways for drug development and clinical evaluation. Clinical studies conducted under an exploratory Investigational New Drug involve administering small amounts of an investigational agent for short periods to a limited number of patients with no therapeutic or diagnostic intent. The results can provide essential pharmacodynamic, pharmacokinetic, and/or imaging data at the initial stage of the clinical trials process to inform and expedite the subsequent development of promising new agents.
Expression Analysis Systematic Explorer (EASE): a computer program used for rapid biologic interpretation of gene lists that result from the analysis of microarray or other high-throughput genomic data. The primary function of EASE is to perform theme discovery for a given list of genes.
expression profiling: the expression of a set of genes in a biologic sample (eg, blood, tissue) using microarray technology.
expression signature classifiers: a diagnostic or prognostic classifier in which the components are genes defined from microarray approaches that have shown differential expression in patients responding to or likely to respond (as a function of risk category) to a given therapeutic intervention and therefore have use in future studies to determine clinical outcomes in patients. Classifiers have to be validated in independent studies and have to have a high negative predictive value to justify withholding a potentially curative therapy. See classifiers.
expressive writing: a brief and simple intervention that may help patients cognitively and emotionally process the cancer experience by prompting participants on several occasions to briefly write about their deepest thoughts and feelings regarding the experience.
extensive metabolizer: metabolic phenotype related to drug metabolizing enzymes, which results in a normal metabolic ratio of a probe drug.
external beam radiation therapy (EBRT): radiation therapy involving a machine that moves around the patient and directs a beam or beams of high-energy X-rays at the patient's tumor.
external validation: the process of validating the classifier obtained from developmental studies using truly independent data external to the study used to develop the classifier. The objective of external validation is to determine whether use of a completely specified diagnostic classifier for therapeutic decision making in a defined clinical context results in patient benefit. For example, an independent validation study could be a prospective clinical trial in which patients are randomly assigned to treatment assignment without use of the classifier versus treatment assignment with the aid of the classifier.
extracapsular lymph node involvement: the extension of cancer beyond the lymph node capsule.
extracellular domain: a portion of any receptor that protrudes out of the membrane on the outside of the cell or organelle. The primary function of this portion of a receptor is to recognize and respond to specific ligand(s).
extracellular matrix (ECM): components that are extracellular and composed of secreted fibrous proteins (eg, collagen) and gel-like polysaccharides (eg, glycosaminoglycans) binding cells and tissues together. In addition, the ECM contains adhesion proteins (eg, fibronectin and laminin) that link components of the matrix both to one another and to attached cells. Depending on the tissue, the composition of the ECM differs. For example, collagen is the primary component of ECM; elastin fibers contain cross-linked elastin; and integrins are cell-surface receptors responsible for the attachment of cells to the ECM.
EZH2: a transcriptional repressor.