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Oncology Glossary

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Rab: a family of GTP-binding proteins related to Ras proteins. Rab proteins regulate vesicular transport in mammalian cells by participating in exocytic and endocytic pathways at specific points.

RAD001: an orally active derivative of rapamycin, RAD001 (also known as everolimus) is an inhibitor of mammalian target of rapamycin. See mammalian target of rapamycin (mTOR).

RAD54L: the protein encoded by this gene has been shown to play a role in homologous recombination related repair of DNA double-strand breaks.

radioimmunoassay: a highly sensitive laboratory technique used to measure minute amounts of substances including hormones, antigens, and drugs in the blood. First, a known amount of the substance to be measured is tagged with a radioisotope, mixed with antibodies to that substance, and added to a sample of the patient’s blood. The same nonradioactive substance in the blood competes with the isotope for binding to the antibodies, thus displacing the radiolabeled substance. The amount of free radioisotope is then measured to determine the level of the original substance in the blood.

radioimmunotherapy/radioimmunodetection: a procedure that uses a radiolabeled antibody for the treatment or detection, respectively, of cancer or other diseases.

Raf: proteins (Raf-1, A-Raf, B-Raf) that are intermediate to Ras and MAPK in the cellular proliferative pathway. Raf proteins are typically activated by Ras via phosphorylation, and activated Raf proteins in turn activate MAPK via phosphorylation. However, Raf proteins may also be independently activated by other kinases.

Raf kinase: an essential component of the MAP kinase pathway, which is a key signaling mechanism that regulates many cellular functions such as cell growth, transformation, and apoptosis. Raf (also known as MAPKK kinase or MAPKKK) can be mutated or overexpressed in certain types of cancer. Raf kinase is a target of inhibition by sorafenib. The regulation of Raf is complex and involves the integration of other signaling pathways as well as intramolecular interactions, phosphorylation, dephosphorylation, and protein-protein interactions.

Raf-MEK-ERK pathway: a phosphorelay system in which the three protein kinases get activated sequentially: activated Raf activates MEK, which activates ERK.

Raf-1-MEK-ERK: signaling pathways involving Raf, MEK, and ERK.

ramucirumab: a fully human monoclonal antibody (also known as IMC-1121B) against vascular endothelial growth factor receptor 2 in the treatment of solid tumors.

Ran: the Ras-related protein in the nucleus. Ran is the major regulator that controls the bidirectional transport of macromolecules between the nucleus and the cytoplasm of cells through the nuclear pore complex in nuclear membranes. It belongs to a family of GTP-binding proteins that function as molecular switches, with the GTP-bound form being the on switch and the GDP-bound form being the off switch.

rapamycin: see sirolimus.

rapamycin-binding protein: intracellular protein that binds immunosuppresants such as rapamycin and tacrolimus. The complex binds to and inhibits the serine/threonine kinase activity of mammalian target of rapamycin.

raptor (regulatory-associated protein of mTOR): a scaffold protein that enhances the ability of mammalian target of rapamycin (mTOR) to activate 4E-BP1 and p70 S6 kinase. Raptor binds to, but does not alter the catalytic activity of, mTOR. However, by also binding 4E-BP1 and p70 S6 kinase, raptor increases the ability of mTOR to phosphorylate p70 S6 kinase.

RARα (retinoic acid receptor): a transcription factor that is constitutively complexed with co-repressor molecules in the absence of its activator, all-trans retinoic acid (ATRA). Binding of ATRA is associated with a conformational change in RARα, which abrogates co-repressor binding sites and exposes co-activator binding sites.

RARβ2 (retinoic acid receptor beta) gene: gene expressed from two distinct promoters, both of which have distinct CpG islands. RARβ2 is expressed in adult tissues and hypermethylated in several cancer cells. Studies in cell lines indicate that sensitivity to the effects of retinoic acid is lost when RARβ expression is suppressed.

RAS: gene family consisting of H-RAS, N-RAS, and K-RAS. The RAS proteins are typically small triphosphate-binding proteins and are the common upstream molecules of several signaling pathways that play a key role in signal transduction, which results in cellular proliferation and transformation.

Ras-MAP kinase cascade: signal transduction pathway involving Ras and MAP kinase. The pathway is generally involved in proliferative and survival signals. See RAS and MAPK (mitogen-activated protein kinase).

Ras pathway: a signal transduction pathway involving the signaling molecules Ras, Raf, and ERK. Activated Ras activates Raf, which then activates MEK (MAPK/ERK kinase) and thereby ERK. Generally, the involvement of these molecules results in enhanced cell survival and/or proliferation.

Ras-Raf-ERK pathway: signal transduction pathway involving the signaling molecules Ras, Raf, and ERK. Activated Ras activates Raf, which then activates MEK (MAPK/ERK kinase) and thereby ERK. Generally, the involvement of these molecules results in enhanced cell survival and/or proliferation. Activating mutations of Raf have been discovered in some human tumors such as melanoma and non–small-cell lung cancer. See Ras, Raf, MAPK (mitogen-activated protein kinase), and ERK (extracellular receptor kinase).

Ras-Raf-MEK-ERK: see Ras, Raf, MEK (MAPK-ERK kinase), MAPK (mitogen-activated protein kinase), and ERK (extracellular receptor kinase).

RASSF1A (Ras association domain family member 1A): one of the most commonly epigenetically silenced tumor suppressor genes in human cancer that controls cell cycle and apoptosis.

Rb: the first tumor suppressor gene identified in children with hereditary retinoblastomas. The phosphorylation state of Rb has important implications for cell cycle progression. Hypophosphorylated RB tightly binds the transcriptional factor E2F (also important for cell cycle regulation), thus preventing E2F-mediated cell cycle entry.

Rb/E2F: see Rb and pRb (Rb phosphorylation).

reactive oxygen species (ROS): molecules like hydrogen peroxide, hydroxyl radical, and superoxide anion that are formed as a consequence of ionizing radiation with biologic molecules, cellular respiration (via the electron transport chain), and a metabolic byproduct of neutrophils and macrophages. The activity of ROS damages cellular molecules and structures. In phagocytic cells, ROS are essential to eliminate harmful agents like bacteria. Cellular enzymes (eg, catalase and superoxide dismutase) and antioxidants (eg, vitamins E and C) dissipate ROS after they are formed.

rearrangement: a genomic alteration resulting from a chromosomal breakpoint that leads to a large structural change in or between chromosomes.

reasonable and necessary care: the standard the US Medicare program has used to determine coverage decisions since the origination of the program in 1965. The reasonable and necessary care standard has played a large impact in determining the care covered by private insurance as well.

receiver operating characteristic (ROC) curves: curves that plot the true-positive rate (sensitivity) against the false-positive rate (1-specificity) for different cutoff levels of a test. The area under the curve is a measure of the accuracy of the test. An area of 1.0 represents a perfect test (all true positives), whereas an area of 0.5 represents a worthless test.

receiver operating characteristic (ROC) curve: curves that plot the true-positive rate (sensitivity) against the false-positive rate (1-specificity) for different cutoff levels of a test. The area under the curve is a measure of the accuracy of the test. An area of 1.0 represents a perfect test (all true positives), whereas an area of 0.5 represents a worthless test.

receptor-enhanced chemosensitivity (REC): synergistic activity of the anti-HER2/neu monoclonal antibody trastuzumab when administered in conjunction with cytototoxic drugs.

receptor tyrosine kinase: transmembrane protein with intrinsic ability to transfer phosphate groups to tyrosine residues contained in cellular substrates. See tyrosine kinase receptors.

recessive: a trait that is expressed only when the determining allele is present in the homozygous condition.

RECIST (Response Evaluation Criteria in Solid Tumors): a model proposed by the Response Evaluation Criteria Group by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment.

RecQ1: gene encoding a protein that is a member of the RecQ DNA helicase family, which comprises enzymes involved in various types of DNA repair.

recurrence-free interval: time from random assignment to documented first recurrence or death resulting from the original cancer.

recurrence score: a number between 0 and 100 that corresponds to a specific likelihood of breast cancer recurrence within 10 years of initial diagnosis. The score is derived from a mathematical function combining the expression values of 16 breast cancer–related genes and five reference genes.

recursive partitioning: multivariable analysis that generates a clinically intuitive decision tree model in which the population is divided into prognostic subgroups. This is achieved through multiple dichotomous divisions on the basis of a set of independent variables.

recursively partitioned mixture model (RPMM): a likelihood-based hierarchical clustering procedure that produces classification solutions similar to those of conventional mixture models in a computationally efficient manner and allows for precise inference regarding potential covariates.

reference normalization: a process of accounting for preanalytic sources of variation in gene expression measurements (eg, sample age, fixative type, duration of fixation) by adjusting expression levels relative to expression of reference genes.

regulatory T cells (suppressor T cells): a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. This is an important self-check built into the immune system so that responses do not become chaotic. Regulatory T cells come in many forms, including those that express the CD8 transmembrane glycoprotein (CD8 T cells); those that express CD4, CD25, and FOXP3 (CD4CD25 regulatory T cells); and other T cell types that have suppressive function. These cells are involved in closing down immune responses after they have successfully tackled invading organisms and also in keeping in check immune responses that may potentially attack one’s own tissues (autoimmunity).

RelA: transcriptional factor present in hematopoietic cells.

REMARK criteria: guidelines for reporting tumor marker studies, which include a statement of objectives and a description of patient population and treatments received, biologic materials, and assay methods. Criteria also include guidelines for reporting data, results, and discussion.

reoxygenation: the effect of radiation that, by reducing interstitial pressure in tumors, allows better oxygen delivery and collapsed blood vessels to reopen.

residual cancer burden (RCB): an index to estimate the extent of residual invasive cancer in the breast and regional lymph nodes after neoadjuvant chemotherapy. RCB combines parameters derived from the review of routine pathology materials: two-dimensional extent of residual primary tumor, proportion of this primary tumor area that contains cancer cells, proportion of the residual primary cancer that is in situ, the number of involved regional lymph nodes, and the diameter of the largest nodal metastasis.

residual risk: risk of relapse after conventional treatment for disease. This differs from prognosis because residual risk does not reflect the natural history of disease but rather the likelihood of a relapse after treatment interventions.

Response Evaluation Criteria in Solid Tumors (RECIST): a model proposed by the Response Evaluation Criteria Group by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment.

retinoblastoma: a malignant tumor of the retina. Heterozygous carriers of a mutant Rb1 allele typically develop bilateral tumors at an early age whereas sporadic retinoblastoma in noncarriers results from the spontaneous inactivation of both alleles in later life.

retinoblastoma protein: see Rb.

retinoid receptors: nuclear receptors for retinoic acid. The functional receptor is a heterodimer of closely related retinoic acid receptor (RAR) and retinoid X receptor (RXR).

retroviral vector: artificial DNA construct derived from a retrovirus and used to insert genetic material into cells.

reverse phase protein array: a high-throughput technique to evaluate the levels of multiple proteins or phosphoproteins in lysates derived from cells or tissues using arrays of antibodies that are specific for a panel of protein targets. This technique can provide a comprehensive assessment of the levels and/or activity of a large number of proteins across different signaling pathways.

reverse-transcriptase polymerase chain reaction (RT-PCR): process used in detecting polymerase chain reaction products as they accumulate that can be applied to gene expression quantification by reverse transcription of RNA into cDNA. Results are usually normalized to an endogenous reference. Current devices allow the simultaneous assessment of many RNA sequences.

revlimid: an agent that belongs to the class of immunomodulatory drugs (IMiDs). Revlimid (also called lenalidomide) is a derivative of thalidomide and has been shown to inhibit multiple pathways that are implicated in multiple myeloma cells interacting with the bone microenvironment.

rhabdomyosarcoma: a malignant solid tumor arising from mesenchymal tissues, which typically differentiate to form striated muscle. Rhabdomyosarcoma is divided into two primary subtypes: the alveolar rhabdomyosarcoma, primarily arising in adolescents and young adults, and the embryonal rhabdomyosarcoma, predominantly affecting infants and children. It is one of the most frequently occurring soft-tissue sarcomas and the most common in children younger than age 15 years, accounting for 6% to 8% of all childhood cancers.

Rheb (Ras homolog enriched in brain): a conserved member of the Ras superfamily of G proteins that promotes cell growth. Rheb activity can be blocked by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR). Thus Rheb is involved in mTOR signaling, a pathway involved in nutrient-mediated signaling.

rho: a family of related proteins that share structural similarity with Ras proteins. They contain a GTPase activity and can bind GTP and GDP. The binding of GTP and GDP is regulated by guanine nucleotide exchange factors.

RhoB: Ras-like small protein with GTPase activity involved in a variety of cellular processes, including cell cycle progression, cellular transformation, and apoptosis. Specific prenylation of Rho proteins is required for Rho functions. See prenylation.

RhoC: gene coding for the RhoC protein. See Rho.

rhodopsin kinase: a special G-protein–coupled receptor kinase expressed in the retina that is involved in quenching light-induced signal transduction in photoreceptors of the eye.

ribosomal proteins: proteins that assemble in an ordered fashion to form the functional ribosome. Ribosomes in eukaryotes are made of large 60S subunits (an ordered assembly of the L proteins) and small 40S subunits (an ordered assembly of the S proteins), forming the functional 80S initiation complex with the mRNA. The number of L and S ribosomal subunits differs in different species.

ribosomal S6 kinase (S6K): member of the class of AGC family of serine/threonine protein kinases, which also includes protein kinase C and protein kinase B. ribosomal S6 kinase (also called p90RSK) activity is regulated by phosphorylation/dephosphorylation events, which occur in response to various stimuli. The two forms of S6K, S6Kα and S6Kβ, have cytoplasmic and nuclear variants and have the highest sequence homology in the kinase and kinase extension domains. See p70S6K/RPS6KA1.

rIL-2: recombinant interleukin-2. See interleukin-2 (IL-2).

RIP1-Tag2 transgenic mouse model: mouse model in which the insulin-producing B cells of the pancreatic islets are engineered to express to simian virus 40 oncogene large and small tumor antigens (Tag). Targeted oncogene expression induces the formation of hyperproliferative islets by the time the mice reach 3 to 4 weeks of age; a subset of the dysplastic islets progress by activating angiogenesis, resulting in angiogenic islets, characterized by endothelial cell proliferation and vascular dilation. Beginning at 10 weeks, a few of the angiogenic islet dysplasias progress into solid tumors and pancreatic neuroendocrine carcinomas that prove lethal in 100% of mice by approximately 15 weeks of age.

risk-adapted treatment stratification: a process by which patient characteristics (clinical, biomarker, molecular, etc) are used to group patients into similar prognostic categories, permitting more accurate assessment of treatment benefit. This may also describe a process by which patient characteristics are used to select the most appropriate treatment, recognizing that more aggressive treatment strategies may be more appropriate for patients at high risk of disease progression and that less aggressive treatment approaches may be tailored to those patients at low risk of progression.

risk adjustment: a strategy that aims to allow for fair comparison of outcomes of different patient samples by statistical compensation for risk factor differences between the samples (eg, case mix in different hospitals).

risk-based screening: screening for long-term and late cancer and cancer treatment–related effects that considers health risks related to the patient (age at treatment, attained age, sex, race, genetics, health behaviors, etc) and cancer (histology; involved sites; specific treatment like surgery, radiation, chemotherapy, hematopoietic cell transplantation, transfusion, etc).

Risk of Ovarian Cancer Algorithm (ROCA): a statistical tool that considers current and past CA-125 values, as well as age, to assign an ovarian cancer risk probability that is then categorized as low, intermediate, and elevated.

risk-reducing salpingooophorectomy: a surgical procedure in which the ovaries and fallopian tubes are removed, intended to reduce the risk of developing ovarian and fallopian tube carcinomas in asymptomatic women who are at increased genetic risk of those neoplasms.

risk score: a simplified version of a prognostic model, in which scores are assigned to each risk factor (eg, on the basis of rounded regression coefficients).

rituximab: a monoclonal antibody therapy that is indicated for relapsed or refractory low-grade or follicular, CD20+, B-cell non-Hodgkin lymphoma.

RIZ1: gene that encodes a retinoblastoma-interacting zinc finger protein. The RIZ1 isoform is lost or expressed at reduced levels in cancer cells. RIZ1 expression is associated with cell-cycle arrest.

RNA polymerase II: the multiprotein complex that carries out transcription, reading the DNA template to yield mRNA.

RNA-Seq: sequencing that determines the nucleotide sequence of RNA as cDNA derived from mRNA typically but also microRNAs or other RNAs. In tumor genomic profiling, RNA-Seq (also called transcriptome sequencing) captures the expressed genome of a sample and can enable robust detection of dysregulated genes, gene fusion events, and alternative splice isoforms.

RNAi (RNA interference): post-transcriptional gene silencing that regulates gene expression. See siRNA (short-interfering RNA).

RNAPc2 (recombinant nematode anticoagulant): an 85–amino acid protein originally isolated from a hematophagus hookworm with known inhibition of the factor VIIa/tissue factor complex.

RNase H: enzyme that cleaves RNA in RNA-DNA hybrids.

Rosa-26 mice: mouse strain developed from murine embryonic stem cells infected with a retroviral gene trap containing the genes for neomycin and beta-galactosidase (lacZ). Rosa-26 mouse strains express lacZ in all hematopoietic cells and cells in all tissues of the embryo. The strain is thus exquisitely suited for chimeric analysis.

RPLPO (ribosomal protein, large, PO): sometimes used as a reference or housekeeping gene for normalization of reverse transcriptase polymerase chain reaction data.

RRM1 (ribonucleotide reductase): a gene that encodes the regulatory subunit of ribonucleotide reductase and is a molecular target of gemcitabine.

RUNX: mammalian homologs of the Drosophila genes runt and lozenge. Members of the RUNX family function as master regulators of hematopoiesis and osteogenesis. They code for a subunit of the transcription factor, PEBP2/CBF (the β subunit consists of the non-RUNX protein PEBP2β).

RUNX1: gene that encodes a subunit of core binding factor, a heterodimeric transcription factor involved in normal hematopoiesis.

RUNX1/MTG8: the t(8;21) chromosomal translocation commonly seen in acute myeloid leukemia that results in the expression of the fusion protein RUNX1/MTG8, which behaves as a transcriptional repressor.

ruxolitinib: a potent inhibitor of Janus-associated kinases 1 and 2 (JAK1/JAK2) that that has shown clinical benefit in patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera (PV) MF, and post-essential thrombocythemia MF; and patients with PV who have had an inadequate response to or are intolerant of hydroxyurea.

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