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Oncology Glossary

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p110α subunit of PI3K: the catalytic subunit of PI3K, denoting its molecular weight. The enzymatic activity of PI3K resides in the p110α subunit. See PI3K (phosphatidylinositol-3 phosphate kinase).

p14ARF: a protein product of the alternative reading frame of the human INK4a locus. p14ARF is a tumor suppressor protein (a cell cycle kinase inhibitor) and acts through p53-dependent and p53-independent pathways. In p53-dependent pathways, by inhibiting cell cycle kinase, p14ARF leads to increased levels of MDM2 and arrests cell cycle progression both at the G1 and G2/M phases. In response to oncogenic stimuli, p14ARF acts by attenuating MDM2-mediated degradation of p53.

p15: see p15INK4b.

p15CDKN2B gene: gene encoding for p15.

p15INK4b: a specific cell cycle regulator that inhibits the G1 phase of the cell cycle by inhibiting the kinase activity of cyclin-dependent kinases 4 and 6. The gene is inactivated by homozygous deletion, point mutation, or methylation in various tumors. See cyclin D.

p16: molecule that binds to cyclin-dependent kinase 4 and 6, thereby preventing their interaction with cyclin D. p16 (also known as p16INK4) behaves as a negative regulator of proliferation and arrests cells in the G0/G1 phase of the cell cycle.

p16CDKN2A: see p16.

p16INK4A: see p16.

p21: see p21Cip1.

p21Cip1: the cyclin-dependent kinase inhibitor p21Cip1 inhibits cell-cycle progression by binding to cyclin/CDK complexes and arresting cells in the G1 phase of the cell cycle.

p21WAF1: see p21Cip1.

p21WAF1/CIP: see p21Cip1.

p27: see Kip1/p27.

p27Kip1: member of the family of cell cycle regulators typically known as cyclin-dependent kinase inhibitors (CDKIs). p27Kip1, like other CDKIs, binds cyclin-CDK complexes, leading to cell cycle arrest in the G1 phase of growth.

p300: a non–DNA-binding transcriptional coactivator. p300 interacts with transcriptional activators as well as repressors to influence cellular processes of growth, terminal differentiation, and apoptosis. p300 has histone acetyl transferase activity.

P38α: a member of the family of MAPKs that is activated by stress and proinflammatory cytokines and is involved in pathways that mediate cell proliferation, differentiation, and survival.

p-4EBP: phosphorylated form of 4EBP. An inhibitor of the eukaryotic initiation factor 4E (eIF4E), 4EBP is responsible for cell cycle arrest. Phosphorylation of 4EBP disrupts its ability to bind eIF4E, thereby enhancing cap-dependent translation initiation.

p53: a transcriptional activator of genes with a p53-binding site and an inhibitor of genes lacking a p53 binding site. Expression of high levels of wild-type p53 is associated with cell cycle arrest and apoptosis. Mutations in p53 are seen in several tumors.

p53: a tumor suppressor gene. The normal function of p53 is to act as a transcriptional activator of genes with a p53-binding site and an inhibitor of genes lacking a p53 binding site. Expression of high levels of wild-type p53 is associated with cell-cycle arrest and apoptosis through induction of P21Waf1/Cip1 and hMdm2. Mutations in p53 are seen in many tumors as well as in the Li-Fraumeni–inherited cancer syndrome.

p53AIP1 (p53-regulated, apoptosis-inducing protein 1): a tumor suppressor gene that localizes to the mitochondria and regulates mitochondrial membrane potential.

p57Kip: member of the family of cell cycle regulators known as cyclin-dependent kinase inhibitors (CDKIs). p57Kip binds to cyclin-CDK complexes, leading to cell cycle arrest. However, unlike other CDKIs, p57Kip functions in a cell type–specific manner.

p57KIP2: see p57Kip

p63: also known as TP63. A member of the p53 gene family. A transcription factor with several isoforms that is involved in normal development and development of malignant cells. Staining for p63 in certain cancer cells can help distinguish normal from malignant cells or the type of cancer cells. p63 is involved in normal skin, stem cell, and cardiac development and in inducing apoptosis in certain settings.

p70 S6 kinase: the kinase responsible for the mitogen-dependent stimulation of the ribosomal protein S6, which regulates the initiation of translation or protein synthesis.

p70S6K/RPS6KA1: gene that expresses a kinase that catalyzes the phosphorylation of the S6 protein, a component of the 40S subunit of the eukaryotic ribosome, which plays a key role in protein synthesis. P70S6K and RPS6KA1 are alternate names given to the same gene.

p73: a relative of p53 that encodes a p53-like protein with a DNA-binding domain that corresponds to that seen in p53. Like p53, p73 is a transcriptional activator and is associated with cell cycle regulation. However, p73 differs from p53 in its inability to respond to DNA damage.

p90 heat shock protein/chaperone: see HSP90.

pack-year: a unit to quantify exposure to cigarette smoke. A pack-year is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years smoked.

pagetoid growth pattern: an intraepidermal growth pattern in which melanocytes are scattered through all layers of the epidermis, typically in small clusters, as opposed to remaining within the basal layer.

PAI-1 (plasminogen activator inhibitor): a serine protease inhibitor and an inhibitor of uPA and tPA. Together with other members of the uPA system, it is involved in extracellular matrix degradation, stimulation of cell migration and control of cell adhesion, which are important for invasion and metastasis in cancer. The official gene symbol is SERPINE1.

paired-end sequencing: sequencing one end of a linear fragment (representative of the original DNA) followed by sequencing the other end. This is different from mate-pair sequencing, in which DNA fragments are circularized before sequencing. Paired-end sequencing allows more accurate mapping or placement of a DNA sequence on a reference genome. In cancer specimens, paired-end sequencing allows the detection of large- and small-scale structural genomic rearrangements.

PAK-JNKK-JNK/JNK activation pathway: a cascade of proteins originally identified as those involved in the activation (by phosphorylating critical residues) of the activation domain of c-Jun, a component of a transcriptional complex. These kinases have also been known to be activated in stress-activated pathways. See JNK/SAPK.

palliative care: care designed to address symptoms and maximize quality of life, regardless of patient prognosis.

pancreatic neuroendocrine tumor (PNET/islet cell tumor): a relatively rare form of pancreatic cancer, in which tumors arise from the pancreatic islets of Langerhans, being composed of transformed islet cells that produce (or once produced) insulin or other polypeptide hormones. The endocrine hormone–secreting islet cells (and islet tumors) express a number of neuronal genes, reflecting an evolutionary heritage with neuronal cells, and hence their designation as neuroendocrine, to contrast them with the prevalent form of human pancreatic cancer (ductal adenocarcinoma).

panitumumab: a fully human immunoglobulin G2 monoclonal antibody (also known as ABX-EGF) against the epidermal growth factor receptor (EGFR) that inhibits ligand-induced activation of EGFR. This antibody is generated from mouse strains engineered to be deficient in mouse antibody production and to produce fully human antibodies.

PAP (prostatic acid phosphatase): a secretory protein produced by cells of the prostate gland.

PARs (protease-activated receptors): a family of seven transmembrane G protein–coupled receptors with four subtypes identified in humans (PAR1-4). PARs are usually activated by thrombin (except PAR2). When the receptor ligand is cleaved, it initiates a cascade of intracellular signaling, which ultimately leads to increased angiogenic activity.

passenger mutation: a somatic mutation present in cancer with no bearing on tumor biology.

pathologic complete response: the absence of any residual tumor cells in a histologic evaluation of a tumor specimen.

patient-centered communication (PCC): communication that helps clinicians provide care according to the patient’s values, needs, and preferences and that allows patients to provide input and participate actively in decisions regarding their health and health care. Patient-centered communication has six critical functions: fostering healing relationships, exchanging information, making decisions, responding to emotions, managing uncertainty, and enabling patient self-management.

patient-derived xenograft (PDX): tumor models created by implanting tumor tissue from a patient directly into an immunodeficient mouse (typically subcutaneously). The goal of patient-derived xenograft models is to propagate tumor cells while preserving the original characteristics of a patient’s tumor to create more clinically relevant tumor models for experimentation.

patient-reported outcomes: questionnaires used in a clinical setting to systemically collect information directly from the patient.

PD 0184264: the active metabolite of CI-1040. See CI-1040.

PD-1: programmed cell death protein 1 (CD279), a receptor expressed on the surface of activated T, B, and NK cells that negatively regulates immune responses, including autoimmune and antitumor responses.

PDCD5 (programmed cell death 5): gene encoding a protein expressed in tumor cells during apoptosis independent of the apoptosis-inducing stimuli. Before apoptosis induction, this gene product is distributed in both the nucleus and cytoplasm. Once apoptosis is induced, the level of this protein increases and, by relocation from the cytoplasm, it accumulates in the nucleus. Although its exact function is not defined, this protein is thought to play an early and universal role in apoptosis. PDCD5 is also called TFAR19 (TF1 cell apoptosis-related gene 19).

PDGF (platelet-derived growth factor): a family of proteins that exists in the A, B, C, or D forms. PDGF is involved in proliferation pathways, especially of mesenchymal cell types. PDGF forms homodimers (eg, AA, BB, CC, DD) or heterodimers (eg, AB), which interact with appropriate cellular receptors.

PDGFR (platelet-derived growth factor receptor): the receptor for PDGF, which exists distinctly as the dimeric αα or ββ form. All dimer combinations of PDGFA and B signal through PDGFR-αα; PDGF BB signals through PDGFR-ββ; PDGF CC signals through the αα and αβ receptors; PDGF DD signals through the ββ and αβ receptors.

PDGFR-α: see PDGFR (platelet-derived growth factor receptor).

PDGFR-β: see PDGFR (platelet-derived growth factor receptor).

PDK1 (phosphoinositide-dependent kinase 1): an activator of AKT. PDK1 interacts with phosphoinositides through its pleckstrin-homology domain, resulting in its recruitment (along with AKT) to the plasma membrane, where it becomes activated (phosphorylated). Once activated, it activates AKT.

PD-L1: programmed cell death 1 ligand 1 (CD274; also known as B7-H1), the major binding partner (ligand) for the PD-1 inhibitory immune receptor. PD-L1 is expressed on the surface of activated antigen presenting cells, such as dendritic cells, and by many types of cancer cells. Its expression is induced by the inflammatory cytokine interferon-γ.

PDPK FA (proline-directed protein kinase FA): a signal-transducing molecule. PDPK FA is essential for the development of highly malignant phenotypes and rapid cancer progression. PDPK FA targets a wide spectrum of oncogenic downstream molecules in a cascading manner.

PDPK (proline-directed protein kinase): protein kinase containing a consensus sequence motif involved in the regulations of a series of cancer events.

pediatric glioblastoma (pGBM): a highly malignant astrocytoma that occurs in children and young adolescents. In contrast to adult GBM, which is a common type of brain tumor in adulthood, pGBM is a rare type of brain tumor in children.

pegylated liposomal doxorubicin (PLD): a unique formulation of conventional doxorubicin (commonly used in the treatment of a wide range of cancers) in which a polyethylene glycol layer surrounds the doxorubicin-containing liposome via a process termed pegylation. Pegylation protects the liposomes from detection by the reticuloendothelial system and increases the plasma half-life of the compound compared with conventional doxorubicin.

penetrance: the likelihood that a given gene mutation will produce disease. This likelihood is calculated by examining the proportion of people with the particular genetic mutation that show symptoms of disease.

pentaplex: a variation of multiplexing or multiplex polymerase chain reaction (PCR) that simultaneously amplifies two or more regions of DNA by virtue of adding more than one primer set to the amplification reaction mixture. In pentaplex PCR, five different segments of DNA are amplified.

peptide targeting: a therapeutic approach in which a peptide is engineered to interfere with the molecular interface between two interacting proteins.

pericytes: fibroblastic/smooth muscle-like cells found in close contact with endothelial cells in small blood vessels and capillaries, where they function as regulators of blood vessel formation and function, in particular contributing to vascular integrity.

peripheral blood mononuclear cell (PBMC): a single-nucleus cell found circulating in the bloodstream that typically includes lymphocytes and monocytes.

peripheral T-cell lymphoma: a group of rare and usually aggressive (fast-growing) non-Hodgkin lymphomas that develop from mature T-cells.

pERK (phosphorylated extracellular signal regulated): phosphorylation of ERK, a downstream enzyme of the MAP kinase pathway that is directly activated by Raf to pERK. In case of Raf inhibition (eg, with sorafenib), the level of pERK serves as a surrogate of this inhibition and could be correlated with response to therapy.

Perl (practical extraction and report language): a programming language especially designed for processing text. Because of its strong text processing abilities, Perl is used extensively in areas such as bioinformatics and Web programming.

permanent-section histology: usually formalin-fixed, paraffin-embedded tissue sections stained by hematoxylin and eosin to reveal metastases. This technique takes an average of 2 to 3 days to complete.

permutation: in statistics, the number of ways to count a set of elements. In performing molecular network analysis from microarray experiments, significance analysis of microarrays (SAM) computes a statistic value for each gene, which is a measure of the strength of the relationship between gene expression and the response variable. To do this, SAM uses repeated permutations of the data to determine whether the expression of any gene is related significantly to the response.

pertuzumab: a humanized monoclonal antibody that binds to HER2 at a site used by the receptor to form dimers with other receptors (the dimerization site) belonging to this family. Signaling via all HER2 dimers is, therefore, inhibited. Also referred to as Omnitarg. See HER2/neu (human epidermal growth factor receptor 2) and ErbB2.

P-glycoprotein (ABCB1): a member of the ATP-binding cassette (ABC) transporters, which are divided into seven subfamilies. ABCB1 is a member of the MDR/TAP subfamily and is involved in multidrug resistance. The protein behaves as a pump and is responsible for the efflux of xenobiotic compounds from the cell, thereby decreasing drug levels in multidrug-resistant cells. Resistance to chemotherapeutic agents in cancer often result from the presence of this transporter.

Pgp (P-glycoprotein): a member of the ATP-binding cassette (ABC) transporters, which are divided into seven subfamilies. ABCB1 is a member of the MDR/TAP subfamily and is involved in multidrug resistance. The protein behaves as a pump and is responsible for the efflux of xenobiotic compounds from the cell, thereby decreasing drug levels in multidrug-resistant cells. Resistance to chemotherapeutic agents in cancer often result from the presence of this transporter.

PHA (phytohemagglutinin): a plant mitogen that nonspecifically activates T-cell and B-cell proliferation and is used in the study of immune mechanisms.

pharmacodynamics: the study of the biochemical and physiologic effects of a drug on the body.

pharmacogenetics: a branch of pharmacology dedicated to understanding the hereditary basis for drug responses related to inherited variations in DNA sequence.

pharmacogenomics: the study of how a person’s genome can affect their reaction to medications.

pharmacokinetics: a branch of pharmacology that studies the relationship between drug exposure level, time course of exposure, and the overall response of an organism. Although pharmacokinetics is largely applied to drugs, it is also applicable to other compounds such as nutrients, toxins, hormones, etc. Pharmacokinetics is subdivided into absorption and disposition (distribution, metabolism, and excretion) and is generally referred to as ADME (absorption, distribution, metabolism, excretion). With respect to drugs administered, all processes occur in tandem once a drug dose is administered. In clinical trials, phase I studies will typically study pharmacokinetics and safety of the drug.

PHAS-1 (phosphorylated heat- and acid-stable protein): another name for 4E-BP1.

phase zero clinical trial: a first-in-human clinical trial conducted under an exploratory IND that has no therapeutic or diagnostic intent and involves very limited human exposure. The results of a phase 0 trial 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 a promising new agent.

PHD domain: a conservative zinc finger-type motif found in plant homeodomains. The PHD domain has been observed as part of transcriptional co-repressor proteins (eg, KAP1), which assist in transcriptional repression.

phenotype: the overall appearance of an organism, or the observable expression of a specific trait, determined by its genotype and environmental factors.

pHER2: phosphorylated (activated) form of HER2.

phosphatidylinositol kinase: generic name for enzymes that phosphorylate phosphatidylinositol.

phospho-AKT: the phosphorylated form of AKT, which is the activated form of the molecule.

phospho-EGFR: the phosphorylated (ie, activated) form of the epidermal growth factor receptor, which is the activated form of the molecule. See EGFR (epidermal growth factor receptor).

phospho-ErbB: the phosphorylated form of ErbB, which is the activated form of the molecule.

phospho-ERK: the phosphorylated form of ERK, which is the activated form of the molecule.

phospho-HER2: phosphorylated form of HER2, which is the activated form of the molecule. See HER2/neu (human epidermal growth factor receptor 2).

phospholipase C: belongs to a family of enzymes known as phosphodiesterases. Phospholipase C cleaves the polar groups from phospholipids (eg, phosphatidylinositol, phosphatidylcholine, phosphotidylserine) and generates diacylglcerol. Thus, phosphatidylinostitol is cleaved into the second messengers, diacylglycerol and inositol-1,4,5-trisphosphate. The different phospholipase C subtypes β, γ, and δ are responsible for activating specific cellular responses.

phospho-MAPK: the phosphorylated form of MAPK, which is the activated molecule. See MAPK (mitogen-activated protein kinase).

phospho-mTOR: the phosphorylated form of the mammalian target of rapamycin, which is the activated form of the molecule.

Phospho-p70 S6 kinase: phosphorylated (active) form of p70 S6 kinase. See p70 S6 kinase.

phospho-PDGFR: the phosphorylated form of platelet-derived growth factor receptor, which is the activated form of the receptor.

phosphorothioate modification: oligonucleotides with a modified phosphodiester backbone that makes them less susceptible to degradation by 3′-exonucleases.

phosphorylation: the addition of phosphate groups from a high-energy compound such as ATP onto small molecules (eg, phosphoinositides) or amino acid residues (eg, serine, threonine, or tyrosine) in proteins. The process is regulated by enzymes called kinases, which add phosphate groups, and enzymes called phosphatases, which remove phosphate groups. The phosphorylation states of individual components in a signal transduction pathway often control the activity of these components, thereby contributing to the overall activation state of signal transduction pathways.

phosphothioate-linked antisense oligonucleotide: the substitution of one oxygen atom with sulfur in the internucleotide link. The phosphothioate modification renders the oligonucleotide more resistant to nuclease degradation without adversely affecting hybridization to complementary sequences.

phosphotyrosine-binding domain: a three-dimensional motif present in proteins that bind to the regions of receptors that have been tyrosine phosphorylated. Thus, tyrosine phosphorylated regions of receptors can be viewed as docking stations for other proteins.

PI3K/AKT pathway: signal transduction pathways involving the signaling molecules phosphatidylinositol-3 kinase (PI3K) and AKT, where PI3K generates phosphorylated inositides at the cell membrane, which are required for the recruitment and activation of AKT, a transforming serine-threonine kinase involved in cell survival. See PI3K (phosphatidylinositol-3 phosphate kinase) and AKT/PKB.

PI3K (phosphatidylinositol-3 phosphate kinase): adds a phosphate group to PI3, which is a downstream signaling molecule involved in survival/proliferative pathways mediated by growth factors such as the epidermal growth factor and the platelet-derived growth factors. PI3K is a heterodimeric molecule composed of a regulatory subunit and a catalytic subunit.

PI3K/PTEN/AKT pathway: signal transduction pathways involving the signaling molecules phosphatidylinositol-3 kinase (PI3K), PTEN, and AKT. PI3K generates phosphorylated inositides at the cell membrane, which are required for the recruitment and activation of the serine kinase AKT. PTEN is a lipid phosphatase that counteracts the effect of PI3K. Accordingly, mutated PI3K and AKT act as dominant oncogenes whereas PTEN is a tumor suppressor gene.

PI3K-AKT-mTOR: indicative of signals being transmitted from PI3K to AKT to mTOR. See PI3K (phosphatidylinositol-3 phosphate kinase), AKT/PKB, and mammalian target of rapamycin (mTOR).

PIK3CA: the catalytic subunit of phosphatidylinositol 3-kinase involved in the generation of PIP3 which, in turn, leads to the activation of AKT and other oncogenic kinases. Mutations in the PIK3CA gene have been found in several cancers, including ovarian, breast, colon, and lung carcinomas. See PI3K and AKT/PKB.

PIK3R3: gene encoding for the regulatory unit of phosphatidylinositol 3 kinase. See PI3K and PIK3CA.

PIM-1 (proviral integration site 1): an oncogene that encodes for a serine/threonine kinase. PIM-1 plays a role in signal transduction in hematopoietic cells by suppressing apoptosis, cell-cycle progression, and transcriptional regulation via chromatin silencing. In all these processes, functions of key target proteins are affected when PIM-1 phosphorylates critical serine/threonine residues.

PIP2 (phosphatidylinositol [4, 5]-biphosphate): an intermediate in the metabolism of phosphoinositides. PIP2 is a substrate for phospholipase C, generating inositol 1, 4, 5-trisphosphate and diacylglycerol, a secondary messenger. It can also be converted by PI3K to phosphatidylinositol, 3, 4, 5-trisphosphate, which can activate kinases that potentiate maximal activity of AKT. In addition, PIP2 facilitates vesicle endocytosis by interacting with proteins with PIP2-binding sites.

PIP3 (phosphatidylinositol-3, 4, 5-trisphosphate): PIP3 is a second messenger in receptor tyrosine kinase signaling. It interacts with the pleckstrin homology domains of Akt and phosphoinositide-dependent kinase 1 (PDK1) and co-localizes them to the plasma membrane where PDK1 activates Akt. The process is augmented by the activation of kinases such as integrin kinase, which is also activated by PIP3. In addition, PIP3 also activates protein kinase C, including those not activated by PIP2, and is involved in T-cell activation, regulating exocytosis, and inducing actin reorganization and membrane ruffling.

PKC theta (PRKCQ): a member of the protein kinase C family. PKC theta is highly expressed by T cells, interstitial cells of cajal and GI stromal tumors.

PKI166: a tyrosine kinase inhibitor that is being developed to target the activities of the ErbB1 and the ErbB2 receptors.

planning target volume (PTV): volume encompassing the clinical target volume that is introduced for radiation treatment planning and evaluation to ensure that the prescribed absorbed dose will actually be delivered to all parts of the clinical target volume with a clinically acceptable probability. It takes into account uncertainties and variations in set-up, positioning, and target motion.

plasmid: a circular, double-stranded unit of DNA that transcribes RNA within a cell independent of the chromosomal DNA.

PLAT: gene encoding for the tissue plasminogen activator, which is used in patients for its anticoagulant activity to prevent the onset of ischemic stroke. Native tissue-type plasminogen activator (t-PA) is a serine proteinase that is activated by plasmin. t-PA has homologies present in other proteins, such as fibronection and epidermal growth factor.

pleomorphic: having the ability to exist in various shapes and forms.

PLGF (placenta growth factor): a protein with significant sequence homology to the vascular endothelial growth factor family of proteins. PLGF has significant expression in the placenta of the developing embryo and is also present on endothelial cells, where its activity contributes angiogenesis induction and endothelial cell permeability.

P-loop of epidermal growth factor receptor: x-ray crystallography studies show that the enzymatic kinase portion of epidermal growth factor receptor is composed of two lobes: the smaller amino terminal N-lobe and the larger carboxy-terminal C-lobe. The phosphate binding loop, or P-loop, is located in the N-lobe. It contains a conserved glycine-rich sequence motif, GXGXXG.

PLZF (promyelocytic leukemia zinc finger) protein: a transcription factor with nine Kruppel-like C2H2 zinc fingers at the C-terminus and a POZ (pox virus and zinc finger) domain at the N-terminus of the protein. The POZ domain mediates dimerization and transcriptional repression. Expressed during development in the central nervous system and the limb buds, PLZF is expressed in CD34+ progenitor cells and in undifferentiated hematopoietic cells in adults. See zinc finger.

PLZF-RARα: a translocation [t(11;17)(q23;q21)] seen in promyelocytic leukemia. The PLZF gene (encoding the promyelocytic leukemia zinc-finger protein) juxtaposes alongside the RAR gene (encoding a retinoic acid receptor). The chimeric protein is a transcriptional repressor.

PMA (phorbol myristate acetate): member of a class of naturally occurring compounds called phorbol esters, which have been used to activate proliferative pathways in cells in the absence of ligands.

pMAPK (phosphorylated mitogen-activated protein kinase): a surrogate to the activated form of the receptor. See MAPK (mitogen-activated protein kinase).

PML-RARα: the acute promyelocytic leukemia chromosomal translocation t(15;17) generates a PML/RARα chimeric gene whose chimeric protein product associates with co-repressor molecules in the absence of all-trans retinoic acid.

Poisson regression analysis: a form of regression analysis based on the assumption that the response variable has a Poisson distribution. Poisson regression can be used when the outcome variable comprises counts, usually of rather rare events (eg, number of cases of cancer over a defined period in a cohort of patients).

poly (ADP-ribose): a negatively charged polymeric macromolecule produced by the poly (ADP-ribose) polymerase (PARP) family of enzymes that is involved in a wide range of biologic processes.

poly (ADP-ribose) polymerase (PARP): a family of nuclear enzymes that facilitate DNA repair via poly (ADP-ribose)ylation of histones and DNA repair enzymes

polycomb protein complexes: chromatin-modifying and -remodeling machinery. These are multimeric complexes that bind to polycomb-responsive elements in genomic DNA. Polycomb complexes are responsible for the gene silencing as a consequence of inducing heterochromatin-like structure in the DNA.

polycomb-group (PcG) repression complex: see polycomb protein complexes.

polymerase chain reaction (PCR): a method that allows logarithmic amplification of short DNA sequences within a longer DNA molecule.

polymerase chain reaction restriction fragment: a procedure to determine single nucleotide polymorphisms (SNPs) on the basis of the different DNA sequence. The small variation in the genetic code for a given SNP ensures that the concrete DNA region becomes a target for a given restriction enzyme; that restriction enzyme does not recognize the sequence in the absence of the change or vice versa. When digesting the amplified DNA fragment with the given restriction enzyme, differently sized DNA fragments are obtained depending on the SNP presence or absence.

polymerase chain reaction restriction fragment-length polymorphism analysis: a technique in which organisms may be differentiated by analysis of patterns derived from cleavage of their DNA. If two organisms differ in the distance between sites of cleavage of a particular restriction endonuclease, the length of the fragments produced will differ when the DNA is digested with a restriction enzyme. Isolation of sufficient DNA for restriction fragment-length polymorphism (RFLP) analysis is time-consuming and labor intensive. However, polymerase chain reaction can be used to amplify very small amounts of DNA, usually in 2 to 3 hours, to the levels required for RFLP analysis.

polymorphic DNA markers: naturally occurring DNA sequence differences among individuals at particular genomic sites that can be used as genetic markers and are commonly referred to as polymorphisms. See single nucleotide polymorphism (SNP).

polymorphism: genetic polymorphisms are natural variations in the genomic DNA sequence present in greater than 1% of the population, with single nucleotide polymorphisms (SNPs) representing DNA variations in a single nucleotide. SNPs are being widely used to better understand disease processes, thereby paving the way for genetic-based diagnostics and therapeutics.

polysomy: at least one more copy of a chromosome than normal (ie, the number of chromosomes is greater than 2 in a cell). Estimates of polysomy are usually not integer values because they are based on the average number of copies across multiple tumor cells between which the number of chromosomes present or often varies.

poor metabolizer: metabolic phenotype related to drug metabolizing enzymes, which results in a slower metabolic ratio of a probe drug compared with an extensive metabolizer.

population-based study: a study in which the patients are drawn from a defined population in a manner that is representative of the source population studied. Such a design can avoid bias arising from the selective factors that guide affected individuals to a particular medical facility, allowing for greater generalizability of the findings.

population stratification: differences in the allele frequencies in populations resulting from differences in ancestry.

positive diagnostic likelihood ratio: ratios that use the sensitivity and specificity of the test used in disease diagnosis to provide a direct estimate of how a test result will change the odds of having a disease. The positive diagnostic likelihood ratio (+DLR) indicates the odds of having the disease when the test is positive and is mathematically defined as the following: +DLR = (test sensitivity)/(1-test specificity).

positive predictive value: the probability of a positive test result being truly positive.

positron emission tomograph–guided induction therapy: a change of treatment for metabolic nonresponders after only a short period (2 weeks) of neoadjuvant chemotherapy, because patients are unlikely to benefit from neoadjuvant treatment, which results in no clinical and/or histopathologic response and no improvement of prognosis. Possible treatment regimens after only 2 weeks of neoadjuvant chemotherapy are immediate resection of the tumor or the integration of chemoradiotherapy to improve local tumor control.

PP2: a commercially available Src kinase inhibitor.

PPARγ: an orphan nuclear receptor belonging to the nuclear hormone receptor family termed peroxisome proliferator activated receptors (PPARs), which are ligand-dependent proteins that stimulate gene transcription. PPARs are activated by peroxisome proliferators (eg, clofibric acid, nafenopin, and some fatty acids). Like other nuclear hormone receptors, PPARγ isoforms heterodimerize with the retinoid X receptor alpha receptor. Synthetic PPARγ ligands include thiazolidinedones, which are known to improve insulin sensitivity.

pRb (Rb phosphorylation): phosphorylated form of Rb, the retinoblastoma susceptibility gene product. Phosphorylated Rb has important ramifications for cell cycle progression. In the phosphorylated state, Rb is unable to bind to the transcriptional factor E2F (which is also important for cell cycle regulation). This results in an excess of free E2F, which can then induce transcription of genes involved in cell cycle progression. Hence, phosphorylation of Rb allows cells to progress through the G1 checkpoint into the S phase of the cell cycle. See Rb.

preanalytic variables: variables that occur before the time that the tissue is fixed in formalin. Most significantly, this includes biologic and artifactual changes to the tissue that occur during the time between the surgical ligation of the oxygen supply and tissue fixation. These are often divided into warm and cold ischemic time variables. However, preanalytic variables also include dozens of other variables beyond time, including room temperature, specimen thickness, surgical technique, transfer methods, etc.

precision medicine: the combination of established clinical/pathologic indices with state-of-the-art molecular profiling to result in diagnostic, prognostic, and therapeutic strategies precisely tailored to each individual patient’s requirements.

predictive biomarkers: measurements associated with response to or lack of response to a particular therapy.

predictive impact: a measurable patient characteristic that is associated with the degree of response to therapy. The predictive impact of a factor refers to that part of its influence on the subsequent course of disease that is attributable to its association with therapy response. The impact of a factor can be prognostic, predictive, or both.

predictive markers: markers, biologic or molecular, that determine which treatment will increase efficacy and improve outcome.

preimplantation genetic diagnosis (PGD): a method used to identify a disease before an embryo is implanted in the uterus.

prenatal diagnosis: a method used to identify a disease while a fetus is in utero.

Prentice criteria: criteria defined by Prentice that a surrogate marker must satisfy to be useful in clinical trials. Treatment must be prognostic (1) for the true end point and (2) the surrogate end point; (3) the surrogate must be prognostic for the true end point, and (4) the full effect of the treatment on the true end point is explained by the surrogate.

prenylation: Ppost-translational lipid modification involving the covalent addition of either farnesyl (15-carbon moiety) or geranylgeranyl (20-carbon moiety) hydrophobic prenyl lipids to a conserved cysteine residue near the C-terminus of a protein. Farnesyltransferases and geranylgeranyltransferases are the respective enzymes that catalyze these reactions.

pretargeted radioimmunotherapy: a multistep targeting procedure that starts by administering an unlabeled bispecific antibody that is given time to localize to the tumor sites. This bispecific antibody is able to bind to the tumor but also has the ability to bind to a small bivalent hapten that can be radiolabeled for use in tumor therapy.

pretargeting: a multistep targeting procedure that starts by administering an unlabeled, modified antibody that is given time to localize to the tumor sites. For targeting radionuclides, bispecific antibodies, or antibodies conjugated to streptavidin, or an oligonucleotide have been used. These modified antibodies are able to bind to the tumor but also have the ability to bind to another small compound that can be radiolabeled for use in tumor imaging or therapy.

PRKCQ: gene that codes for protein kinase C θ, a member of the family of serine-specific and threonine-specific protein kinases that are activated by calcium and the second messenger, diacylglycerol.

proangiogenic factors: factors involved in the process of angiogenesis. Proangiogenic factors constitute growth factors and cytokines, including vascular endothelial growth factors, platelet-derived growth factor, fibroblast growth factor, transforming growth factor-α, epidermal growth factor, hepatocyte growth factor, angiopoietins, and interleukin-8.

proband: the individual under investigation, the index case. In family studies, the individual who is the initial member of a family under investigation.

pro-caspase-9: the inactive form of caspase 9 that has to be proteolytically cleaved to the active caspase 9, which activates caspase-3, leading to DNA fragmentation and cell death. Phosphorylation of pro-caspase-9 by AKT inhibits the proteolytic processing of pro-caspase-9.

prodrug: a drug that is given in an inactive form and is bioactivated to a pharmacologic drug by one or more metabolic processes.

profiling of gene expression: identifying the expression of a set of genes in a biologic sample (eg, blood, tissue) using microarray technology.

progesterone receptor (PgR): nuclear proteins that are activated by the hormone progesterone in breast cancer cells that are hormone-dependent. See estrogen receptor (ER).

prognostic factor: a measurable patient characteristic that is associated with the subsequent course of disease (whether or not therapy is administered). The identification of a prognostic factor does not necessarily suggest a cause-and-effect relationship. However, within a suitable outcome model, the measurement of a prognostic factor contributes to an estimate of an outcome probability (eg, the probability of disease-free survival within a given time interval).

prognostic marker: a marker that predicts the prognosis of a patient (eg, the likelihood of relapse, progression, and/or death) independent of future treatment effects. A factor can be both prognostic and predictive.

prognostic model: a combination of patient, tumor, and treatment characteristics that predict the outcome of individual patients.

progression-free survival: time from random assignment until death or first documented relapse, categorized as either locoregional (primary site or regional nodes) failure or distant metastasis or death.

promoter hypermethylation: methylation of the promoter region of a gene, which can lead to DNA silencing as a consequence of the inability of activating transcriptional factors to bind to the promoter region, a process important in gene transcription. In addition, repressor complexes may be attracted to sites of promoter methylation, leading to the formation of inactive chromatin structures.

promoter methylation: see promoter hypermethylation.

propensity score analyses: a statistical technique to estimate the effect of receiving a treatment when random assignment of treatments is not feasible. Propensity is defined as an individual's probability of being treated with the intervention of interest, given the complete set of information available about that individual. The propensity score provides a single metric that summarizes all of the information available from explanatory variables (eg, confounders). Several different techniques exist, including matching, stratification, and inverse probability weight.

proportional hazards: semiparametric approach to survival analysis developed by Cox in 1972. Unlike product-limit (Kaplan-Meier) survival analyses, which are restricted to categorical predictor variables and do not produce a risk estimate, proportional hazards models can accommodate continuous and ordinal variables as well as allow for the inclusion of multiple predictor variables to compute adjusted risk estimates. Proportional hazards models are based on the fundamental premise that all individuals have the same baseline hazard that varies as a function of time [(t)], but that exposure to the independent variable changes the hazard by a fixed value [h(x)]. What is parameterized in the model is the value of this fixed effect per unit increase of the predictor variable whereas the value of (t) remains uncharacterized.

proportional reduction (in risk): the relative reduction in risk of a clinical outcome (eg, cancer recurrence), attributable to a therapeutic intervention and calculated as 1 − (risk in treated patients/risk in untreated patients). For example, if the 5-year risk of recurrence is 30% for untreated patients and 20% for patients treated with a specific therapy, the proportional reduction is 1 − (20/30) = 0.33 or 33%. Similarly, if the recurrence risk is 15% for untreated and 10% for treated patients, the proportional benefit is 1 − (10/15) = 0.33 or 33%. Note, that in both examples the proportional reduction is the same, whereas the absolute benefit (30% − 20% = 10% and 15% − 10% = 5%) is different.

pro-Ras: Ras protein to which proline has been added, making the protein more hydrophobic and allowing for its targeting to a hydrophobic region in cell membranes. The first step in this process is the farnesylation of Ras.

prospectively defined: refers to a study design (eg, study objectives, outcome measures, analytical methods, analysis plan) specified and documented prior to study conduct. Prospective definition of the study design and analysis plan is critical to produce level-1 evidence for clinical use of a biomarker as defined by Simon et al (Simon RM, et al: J Natl Cancer Inst 101:1446-1452, 2009).

prostaglandin: member of the class of eicosanoids that are derived from fatty acids and are formed via the cyclooxygenase or lipooxygenase pathways. Acting as second messengers and known to predominantly be involved in muscle contraction, prostaglandins have diverse functions, dependent on the cell types.

prostate-specific antigen (PSA): a protein produced by cells of the prostate gland. The blood level of prostate-specific antigen (PSA) is used as a tumor marker for men who may be suspected of having prostate cancer. Most physicians consider 0 to 4.0 ng/mL to be the normal range. Levels of 4 to 10 and 10 to 20 ng/mL are considered slightly and moderately elevated, respectively. PSA levels have to be complemented with other tests to make a firm diagnosis of prostate cancer.

prostate-specific antigen decrease/increase: the relative difference between the nadir/zenith prostate-specific antigen value during the study period and the baseline value.

prostate-specific antigen doubling time: the calculated time for the serum prostate-specific antigen of a patient to double in value.

protease inhibitor (HIV): inhibitors used in combination with NRTI and/or NNRTI to inhibit the replication of HIV in infected cells by blocking the maturation of HIV proteins necessary for HIV survival, thus decreasing viral loads.

proteasomal degradation: see proteasome.

proteasome: a cylindrical shaped supramolecular unit assembled from structural proteins (the cylindrical core) and regulatory proteins (core particles at each end of the cylinder). Proteins targeted for degradation are ubiquinated (see ubiquitin), bind to the core particles, and are degraded as they pass through the cylinder of the proteasome.

protein kinase: generic name for enzymes that transfer a terminal phosphate group from ATP to proteins.

protein kinase C: protein kinase with regulatory and catalytic domain residing on opposite ends of the molecule. Protein kinase C transfers a phosphate group from ATP to an amino acid. When activated, protein kinase C becomes membrane located long after the activation signal has passed. With at least 10 members currently known, protein kinase C has specific requirements for its activity, including Ca2+, diacylglycerol, and a phospholipid.

protein-protein interaction domains: a modular structure present in transcription factors that interacts with other accessory proteins.

protein tyrosine binding domain: see tyrosine kinase domain.

protein tyrosine kinases: generic name for enzymes that phosphorylate tyrosine molecules in proteins.

proteomics: a growing field that uses technologies like electrophoresis and mass spectrometry to identify and quantify cellular proteins that may be expressed, even in small amounts, and to determine their role in the physiologic and pathophysiologic conditions of an individual.

Ψ-CRIP packaging cell line: derived from NIH-3T3 cells, which provide the viral gag, pol, and env proteins of Moloney murine leukemia virus (MoMuLV). The safety features constructed in this packaging line prevents the encapsidation and mobilization of RNA molecules encoding viral structural gene products. Replication-defective tranducing particles are thus generated from the MoMuLV long terminal repeat sequences used to generate full-length RNA needed to generate viral particles and a subgenomic micro-RNA analogous to the MoMuLV env micro-RNA, responsible for the generation of the transgene that is constructed in the vector.

psychosexual: of or relating to the mental, emotional, and behavioral aspect of sexual development and sexual activity.

psychosocial: the psychological (emotional) and social aspects of a disease and its treatment. Some of the psychosocial aspects of cancer are its effects on patients' feelings, moods, beliefs, the way they cope, and relationships with family, friends, and coworkers.

pTAT motif: an 11 amino acid–sequence present in the transcriptional transactivator TAT of HIV type 1 that acts as a protein transduction domain. Engineering proteins containing the pTAT motif allows for their efficient targeting to the cellular nucleus. See PTD (protein transduction domain).

PTCH1 (patched 1): a receptor for three hedgehog ligands (sonic, desert, and Indian hedgehogs). PTCH1 represses the activity of smoothened (SMO). Upon the binding of hedgehog ligands, it releases the inhibition on SMO activity. SMO activates the hedgehog signaling pathway, which is important in cell proliferation and differentiation during embryonic development and tumorigenesis.

PTD (protein transduction domain): small peptide domains that, when linked to other proteins, allow the other proteins to efficiently cross cell membranes.

PTEN (phophatase and tensin homolog): a tumor suppressor gene with a gamut of regulatory activities. The gene product is a multifunctional molecule. The predominant activity identified for PTEN is its lipid phosphatase activity that converts inositol trisphosphates into inositol bisphosphates, thus inhibiting survival and proliferative pathways that are activated by inositol trisphosphates. PTEN acts to maintain arrest in the G1 phase of the cell cycle and enable apoptosis through an AKT-dependent mechanism.

PTK787/ZK222584: a small molecule that inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and platelet-derived growth factors.

PTPRγ (protein tyrosine phosphatase receptor γ): a tumor suppressor gene frequently deleted in renal cell carcinoma and lung cancer. PTRPγ codes for a protein belonging to the protein tyrosine phosphatase family. Members belonging to this family regulate cellular processes of growth, differentiation, mitosis, and oncogenic transformation. The protein coded by PTPRγ possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains and has the enzymatic activity of removing phosphate groups from proteins that regulate biologic processes.

PTPRN2: a putative tumor suppressor gene coding for protein tyrosine phosphatase, receptor type, N polypeptide 2 (also referred to as islet cell antigen-related protein tyrosine phosphatase [IAP], phogrin or protein tyrosine phosphatase, receptor-type Π [PTPR Π]). The enzyme coded by PTPRN2 removes phosphate groups from tyrosine residues in proteins and is a known autoantigen in type I insulin-dependent diabetes mellitus.

PTPRO: a tumor suppressor gene coding for protein tyrosine phosphatase receptor-type O. Gene silencing of PTPRO has been seen in tumors, including lung cancer. The enzyme coded by PTPRO removes phosphate groups from tyrosine residues in proteins.

purine analog: antimetabolites that mimic the structure of naturally occurring purines.

p-VEGFR-2 (phosphorylated vascular endothelial growth factor receptor 2: the activated form of vascular endothelial growth factor receptor 2 (VEGFR-2). VEGFR-2 contains seven immunoglobulin-like loops extracelluarly and split tyrosine kinase domains in the intracellular domain. Upon binding of the ligand vascular endothelial growth factor, VEGFR-2 undergoes autophosphorylation on tyrosine residues located in the cytoplasmic part, and activates several signaling pathways that ultimately lead to angiogenesis and endothelial cell proliferation. Many tumors express VEGFR-2 and the activated form, p-VEGFR-2.

pyrosequencing: a direct DNA sequencing technique based on sequencing by synthesis. Nucleotide signals are detected by release of pyrophosphate upon nucleotide incorporation. Pyrosequencing is frequently used for (targeted) genomic resequencing but also for quantitative detection of DNA methylation by sequencing of bisulfate-converted DNA.

pyruvic acid (pyruvate): an organic acid that is involved in the Kreb's cycle (citric acid cycle) and plays a critical role in ATP generation.

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