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FPP/MSS > Oncology > Flashcards

Oncology Flashcards

1
Q

mechlorethamine

A

class: alkylating agent - cell cycle nonspecific
MoA: bifunctional alkylating agent - produces DNA cross-links, highly reactive/short half-life
uses: Hodgkin’s and non-Hodgkin’s lymphoma, breast, lung, and ovarian cancer
side effects: nausea/vomiting, myelosuppression, mild alopecia

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2
Q

cyclophosphamide

A

class: alkylating agent - cell cycle specific, phase nonspecific
MoA: activated by P450s to phosphor amide mustard, alkylates DNA, does not penetrate CNS well
uses: cancer (broad-spec - most widely-used alkylating agent)
side effects: nausea/vomiting, alopecia, sterile hemorrhagic cystitis (prevented by co-Tx with mesna)

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3
Q

carmustine (BCNU)

A

class: alkylating agent - cell cycle nonspecific
MoA: alkylates DNA, penetrates CNS very well
uses: brain neoplasms, multiple myeloma, melanoma
side effects: nausea/vomiting, delayed myelosuppression

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4
Q

methotrexate (MTX)

A

class: antimetabolite - S-phase specific
MoA: dihydrofolate analog, binds and inhibits dihydrofolate reductase to prevent formation of tetrahydrofolate, interferes with purine and pyrimidine synthesis
uses: acute lymphocytic leukemia, choriocarcinoma
side effects: intestinal epithelium damage, myelosuppression, renal tubular necrosis (tx: urine alkalization), displaces other drugs from serum albumin; some side effects alleviated by co-Tx with leucovorin (folinic acid)

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5
Q

fluorouracil (5-FU)

A

class: antimetabolite - S-phase specific
MoA: pyrimidine analog, activated to F-UTP (inhibits RNA synthesis) and F-dUTP (interferes with thymidylate synthase and DNA synthesis)
uses: broad-spec - colon, breast, stomach, pancreas, ovary, head/neck, bladder, basal cell carcinoma
side effects: nausea, anorexia, diarrhea, myelosuppression (delayed)

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6
Q

cytarabine (Ara-C)

A

class: antimetabolite - S-phase specific
MoA: pyrimidine analog, competes for phosphorylation of cytidine and incorporation into DNA (rate-limiting step: conversion to ara-CMP by deoxycytidine kinase), induces DNA chain termination; short half-life
uses: acute leukemias (i.e. acute myelocytic leukemia), lymphomas, head/neck cancer
side effects: myelosuppression, neurotoxicity

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7
Q

mercaptopurine

A

class: antimetabolite - S-phase specific
MoA: purine analog, converted by cells to ribonucleotide, inhibits RNA and DNA synthesis; cleared by thiopurine methyltransferase (TMPT), nonfunctional TMPT alleles require dose adjustment/alternative Tx
uses: acute leukemias, chronic granulocytic leukemia
side effects: myelosuppression, vomiting, nausea, anorexia, jaundice

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8
Q

hydroxyurea

A

class: antimetabolite - S-phase specific
MoA: substituted urea, inhibits ribonucleotide reductase, blocks conversion of ribonucleotides to dNTPs/DNA synthesis, arrests cells at G1/S interface, most useful in conjunction with radiation (prevents repair of radiation-induced DNA damage)
uses: granulocytic leukemia
side effects: myelosuppression, GI disturbances

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9
Q

vincristine

A

class: vinca alkyloid (natural) - M-phase specific
MoA: binds tubulin, blocks polymerization, inhibits proper microtubule/mitotic spindle formation, arrests cells in metaphase
uses: acute lymphocytic leukemia, lymphomas, Wilm’s tumor, neuroblastoma
side effects: alopecia, neuromuscular abnormalities, peripheral neuropathy

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10
Q

vinblastine

A

class: vinca alkyloid (natural) - M-phase specific
MoA: binds tubulin, blocks polymerization, inhibits proper microtubule/mitotic spindle formation, arrests cells in metaphase
uses: lymphomas, breast cancer
side effects: myelosuppression, epithelial ulceration

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11
Q

paclitaxel (Taxol)

A

class: taxane (natural) - G2-phase specific
MoA: binds beta-tubulin, enhances assembly and stability of microtubules, arrests cells at G2/M interface (this phase is more sensitive to radiation, drug can be used as radiosensitizer), interferes with DNA repair (synergistic with cisplatin or cyclophosphamide); only tumors with high TGF-beta1 respond
uses: refractory ovarian cancer, breast cancer
side effects: myelosuppression, peripheral neuropathy, myalgia/arthralgia, hypersensitivity to detergent (Cremaphor EL)

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12
Q

doxorubicin (ADR)

A

class: antibiotic - cell cycle specific, phase nonspecific
MoA: DNA intercalator, generates ROS/promotes lipid peroxidation, binds DNA/topoisomerase II complex, some anti-angiogenic properties; one of the most active anti-tumor agents
uses: wide-spec - lymphomas, breast, ovary, small cell lung cancer
side effects: dilated cardiomyopathy (dose-related and cumulative, can be lessened by dexrazoxane), myelosuppression, alopecia, GI problems

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13
Q

bleomycin (BLM)

A

class: iron-containing glycopeptide - G2/M-phase specific
MoA: requires chelated Fe for activity - binds DNA, causes oxidative-like damage, induces single- and double-stranded DNA strand breaks; inactivated by bleomycin hydrolase (low levels in lung and skin)
uses: germ cell tumors of testes and ovaries, head/neck, lung cancer, lymphomas
side effects: minimal myelosuppression, pulmonary toxicity (pneumonitis, fibrosis; dose-related and cumulative), skin vesiculation/hyperpigmentation

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14
Q

etoposide (VP16)

A

class: semisynthetic, derived from May apple or mandrake plant - G2-phase specific
MoA: irreversibly stabilizes DNA-topoisomerase II complexes, causes sDNA breaks that cannot be repaired, arrests cells at G2/M interface
uses: lymphomas, acute leukemia, small cell lung cancer, testicular cancer
side effects: myelosuppression, nausea, vomiting, diarrhea, alopecia

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15
Q

filgrastim (G-CSF)

A

class: biological response modifier
MoA: granulocyte colony stimulating factor (G-CSF); limits chemotherapy-induced neutropenia, promotes neutrophil progenitors, expands neutrophil population
uses: chemotherapy palliation
side effects: bone pain

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16
Q

trastuzumab (Herceptin)

A

class: humanized monoclonal Ab
MoA: binds HER2 receptor (human epidermal growth factor), blocks cell proliferation, may elicit immune response against HER2+ cells
uses: HER2+ breast cancer (only responds to trastuzumab, doxorubicin, paclitaxel), other HER2+ cancer (i.e., gastroesophogeal)
side effects: cardiomyopathy, hypersensitivity, infusion reaction (fever, chills)

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17
Q

cisplatin

A

class: platinum coordination complex - cell cycle specific, phase nonspecific
MoA: activated via hydrolysis, causes DNA intrastrand and interstrand crosslinks, covalently binds/inhibits thioredoxin reductase (TrxR), directly promotes apoptosis
uses: wide-spec - testicular, ovarian, head/neck, bladder, small cell lung, colon, esophageal cancer
side effects: nephrotoxicity, ototoxicity, peripheral neuropathy, electrolyte disturbances, nausea, vomiting, mild to moderate myelosuppression

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18
Q

procarbazine

A

class: atypical alkylating agent
MoA: activated by liver microsomal enzymes to methylating agent, causes chromosomal damage, greatest effects in G1 and S phase; no cross-resistance with other alkylating agents
uses: Hodgkin’s lymphoma
side effects: myelosuppression, nausea, vomiting

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19
Q

prednisone

A

class: steroid
MoA: binds steroid receptors, arrests cells at G1, depresses expression of growth-related genes, induces nucleases that modulate cell lysis, anti-emetic, appetite stimulant, anti-inflammatory, good for combination therapy
uses: lymphoma, lymphocytic leukemia, breast cancer
side effects: immunosuppression, weight gain, fluid retention, psychologic effects

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20
Q

tamoxifen (TAM)

A

class: nonsteroidal antiestrogen
MoA: activated by CYP2D6, competitively blocks estrogen receptors in breast tissue, estrogen agonist in bone tissue, elevates sex hormone-binding globulin (decreases free estradiol levels); cytostatic, arrests cells in G0/G1
uses: advanced post-menopausal breast cancer, metastatic pre-menopausal breast cancer, breast cancer prophylaxis for high-risk women
side effects: nausea/vomiting, menopause-like symptoms (i.e. hot flashes, vaginal bleeding/discharge), fatigue, bone/musculoskeletal pain

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21
Q

raloxifene

A

class:
MoA:
uses:
side effects:

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22
Q

letrazole

A

class: nonsteroidal antiestrogen
MoA: irreversibly binds heme group of aromatase (CYP19), estrogen synthesis from androgens
uses: advanced or metastatic post-menopausal breast cancer (first-line)
side effects: nausea/vomiting, menopause-like symptoms (i.e. hot flashes), fatigue, bone/musculoskeletal pain

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23
Q

leuprolide

A

class: steroid
MoA: GnRH analog, initially stimulates LH/FSH but desensitizes GnRH signaling after 2-4 weeks
uses: advanced hormonally-responsive prostate cancer (first-line)
side effects: hot flashes, impotence

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24
Q

flutamide

A

class: nonsteroidal antiandrogen
MoA: blocks androgen receptors
uses: metastatic prostate cancer (in combination with GnRH agonist or second-line)
side effects: gynecomastia, diarrhea, hepatotoxicity

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25
Q

multi-drug resistance (MDR)

A

mediated by ATP-depended drug efflux pumps; common genes include P-glycoprotein (PgP, MDR1), multi-drug resistance proteins (MRP1, 2, 3, 6, 7); especially big issue for vinca alkaloids, doxorubicin, bleomycin, etoposide, paclitaxel

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26
Q

sequential blockade

A

simultaneous action of two inhibitors acting on different steps of a linear metabolic pathway (i.e. hydroxyurea + cytarabine, methotrexate + 5-FU)

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27
Q

concurrent inhibition

A

inhibitors that block two separate pathways which lead to the same end product

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28
Q

complementary inhibition

A

use of one drug that affects the function of an end product and another drug that affects the synthesis of that end product (i.e. cytarabine + doxorubicin)

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29
Q

rescue

A

“rescue” of the patient’s normal cells from chemotherapy; i.e., methotrexate + leucovorin or autologous bone marrow/stem cell transplant

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30
Q

synchronization

A

inducing cells to enter one phase of the cell cycle, then using a drug that is specific for that phase (i.e., low-dose 5-FU to block in S-phase, then high-dose cytarabine to kill in S-phase)

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31
Q

recruitment

A

bring cells out of G0 and back into cell cycle; first treat with cell cycle nonspecific drugs (i.e. mechlorethamine or carmustine), then treat with cell cycle-specific drugs

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32
Q

immunoscore

A

a measure of the presence of activated T-cells in and at the margins of a tumor; presence of more T-cells is prognostic of better survival

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33
Q

adoptive cell transfer

A

treatment of a tumor by injection of ex vivo-expanded tumor-experienced T-cells

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34
Q

IL-12

A

produced by dendritic cells, activates NK cells

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35
Q

IL-2

A

produced by Th1 cells, promotes T-cell survival and proliferation

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36
Q

indoleamine 2,3-dioxygenase (IDO)

A

enzyme expressed by many tumors; converts L-tryptopha to N-formylkynurenine, an immunosuppressive molecule; allows a tumor to suppress host anti-tumor immune responses

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37
Q

arginase

A

enzyme expressed by many tumors; breaks down/depletes arginine, which is required for T-cell activation and survival; allows a tumor to suppress host anti-tumor immune responses

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38
Q

iNOS

A

enzyme expressed by many tumors; produces reactive oxygen and nitrogen species, which may nitrocylate TCRs and inhibit their efficacy; allows a tumor to suppress host anti-tumor immune responses

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39
Q

neoplasia

A

an abnormal mass of tissue, the growth of which exceed and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change

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40
Q

benign

A

a tumor that resembles normal tissue, grows slowly, is non-invasive/encapsulated/well-demarcated, and does not metastasized; named with suffix “-oma”

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41
Q

malignant

A

a tumor of variable morphology, variable growth rate (generally faster than normal tissue), has an invasive growth pattern, and is capable of metastasizing; cancer; named as a carcinoma or sarcoma

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42
Q

tumor

A

swelling; often used interchangeably with “neoplasia”

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43
Q

epithelial

A

tissues that cover surfaces, tubules, and ducts; tumors that originate in this tissue are termed carcinomas

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44
Q

mesenchymal

A

connective tissues; tumors that originate in this tissue are termed sarcomas

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45
Q

differentiation

A

extent to which tumor cells morphologically and functionally resemble the normal tissue counterpart

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46
Q

carcinoma

A

cancer originating in epithelial tissue

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47
Q

sarcoma

A

cancer originating in mesenchymal tissue

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48
Q

adenoma

A

benign tumor

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49
Q

fibro-

A

prefix describing a tumor originating in fibroblasts

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50
Q

IL-10

A

anti-inflammatory cytokine produced by M2 macrophages (often induced by tumor cytokines)

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51
Q

IL-6

A

released by macrophages, may induce chronic inflammation

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52
Q

prostaglandin E2 (PGE2)

A

immunosuppressive signaling molecule produced by many tumors

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53
Q

CTLA-4

A

immunosuppressive receptor found on activated T-cells that, when engaged with ligand B7, induces T-cell suppression/apoptosis; in normal immune response, facilitates downregulation of activated T-cells to prevent autoimmunity

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54
Q

PD-1

A

immunosuppressive receptor found on T-cells; when engaged with ligand, is a negative signal for T-cell activation

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55
Q

PD-L1

A

immunosuppressive ligand for PD-1 that is upregulated on many tumor cells; inhibits T-cell activation through engagement with PD-1

56
Q

reactive oxygen species

A

released by macrophages, may induce chronic inflammation

57
Q

myeloid suppressor cell (MDSC)

A

a particular granulocyte(includes PMNs) or macrophage phenotype that is the major driver of an immunosuppressive tumor microenvironment; may secrete IDO, organize, IL-10, TGF-beta, PGE2, etc.

58
Q

tumor associated macrophage (TAM)

A

macrophage found in the tumor microenvironment; may be induced by the tumor into a myeloid suppressor cell phenotype

59
Q

reactive oxygen species (RNOS, ONOO-)

A

released by macrophages, may induce chronic inflammation; also released by many tumors, may nitrocylate TCRs

60
Q

interferon gamma (IFN-gamma)

A

produced by delta-gamma T-cells and NK cells, induces dendritic cell activation and maturation

61
Q

tumor necrosis factor (TNFalpha)

A

produced by delta-gamma T-cells

62
Q

IL-4

A

produced by Th2 cells, immunosuppressive in the tumor microenvironment

63
Q

IL-13

A

produced by Th2 cells, immunosuppressive in the tumor microenvironment

64
Q

vascular endothelial growth factor (VEGF)

A

growth factor critical for tumor angiogenesis; antagonized by bevacizumab (Avastin)

65
Q

epidermal growth factor receptor 2 (Her2/Neu, ERBB2)

A

receptor for epithelial growth factor often targeted in cancer treatment by trastuzumab (Herceptin)

66
Q

lipo-

A

prefix describing a tumor originating in adipocytes

67
Q

leio-

A

prefix describing a tumor originating in smooth muscle cells

68
Q

rhabdomyo-

A

prefix describing a tumor originating in skeletal muscle cells

69
Q

osteo-

A

prefix describing a tumor originating in bone tissue

70
Q

chondro-

A

prefix describing a tumor originating in cartilage

71
Q

angio-

A

prefix describing a tumor originating in blood vessels

72
Q

mixed tumor

A

a tumor with multiple morphological components; both epithelial and mesenchymal origin

73
Q

teratoma

A

predominantly benign tumors; originate from totipotent stem cells, composed of tissue derived from multiple germ layers

74
Q

carcinosarcoma

A

mixed tumor of both epithelial and mesenchymal cell origin

75
Q

hamartoma

A

a mass of disorganized, mature tissue that is specific to the site of development; indicative of anomalous development (common in stomach, lung)

76
Q

choriostoma

A

a mass of ectopic tissue in a foreign location; i.e., gastric heterotopia (island of gastric mucosa in the colon)

77
Q

ipilimumab (Yervoy)

A

anti-CTLA-4 mAb often used in cancer treatment to enhance host immune response against tumor cells/block T-cell inactivation by tumor cells; more toxicity than pembrolizumab

78
Q

nivolumab

A

anti-PD-1 mAb used in cancer treatment to enhance host immune response against tumor cells/block T-cell suppression by tumor cells

79
Q

pembrolizumab (Keytruda)

A

anti-PD-1 mAb often used in cancer treatment to enhance host immune response against tumor cells/block T-cell suppression by tumor cells; less toxicity than ipilimumab

80
Q

antibody-dependent cellular toxicity

A

mediated by NK cells via CD16 recognition of IgG Fc domains/IgG specificity for tumor cell antigens; also mediated by macrophages and T-cells; stimulated by administration of mAbs in cancer treatment

81
Q

chimeric antigen receptor (CAR)

A

a genetically-engineered receptor often introduced into TILs for adoptive cell transfer that has both an antibody component that is specific for a particular tumor cell antigen as well as a TCR signaling component that is connected to T-cell activation pathways; induces all T-cells in culture to be specific for that cancer antigen (in addition to their native antigens); only effective in hematologic cancers

82
Q

tumor-infiltrating lymphocytes (TIL)

A

T-cells isolated and cultured from a patient’s tumor that has been surgically resected, which are then activated and expanded using a cytokine mix and reinfused into the patient following conditioning (via chemotherapy or radiation)

83
Q

cancer vaccine

A

experimental method of using tumor cells, allogeneic tumor cells, genetically modified APCs, or cancer antigens/proteins in order to vaccinate a patient against cancer cells

84
Q

allogeneic hematopoietic stem cell transplant

A

transplantation of donor hematopoietic stem cells, sometimes along with donor T-cells, in order to replace cancerous blood cells; when T-cells are included, they may react against host antigens, which may cause GVHD or may also attack residual host tumor cells

85
Q

graft vs. leukemia

A

when donor T-cells are included in an HSCT and allowed to react against host cells so that they can kill residual tumor cells; often induces complete remission

86
Q

tumor grade

A

a system of rating a tumor to indicate how much it resembles normal tissue; cellular metrics include cellular/nuclear pleomorphism, coarsely-clumped chromatin, hyperchromatic nuclei, high nuclear to cytoplasmic ratio, large nucleoli, atypical/bizarre mitoses, loss of tissue polarity, and tumor giant cells

87
Q

anaplasia

A

complete lack of tissue differentiation; describes a tumor that lacks any resemblance to parent tissue; can make it difficult to determine tissue origin of metastases

88
Q

local invasion

A

when a tumor has penetrated the basement membrane and invaded the extracellular matrix; involves loss of E-cadherin function, degradation of basement membrane via MMPs, change of attachments (loss of interns), and migration

89
Q

metastasis

A

migration of malignant cells to tissues/organs outside their parent tissue; common sites of metastasis include lymph nodes, lungs, liver, bone, and brain; each tumor type has a penchant for specific metastatic sites based on adhesion molecules and chemokines expressed

90
Q

carcinoma in situ

A

malignant/dysplastic epithelial tissue characterized by full-thickness dysplasia that has not yet invaded its basement membrane

91
Q

dysplasia

A

disordered growth, i.e. loss of polarity, loss of maturation, loss of architecture, loss of organization

92
Q

sentinel lymph node

A

the first lymph node to receive drainage from the site of a tumor; useful to resect and stain to look for first metastases (particularly in carcinomas)

93
Q

clinical stage

A

describes the severity of a cancer, including the magnitude/size of the primary tumor and the extent of spread in the body; TNM staging includes tumor size, nodal involvement, and metastasis; metrics are combined to determine “overall” stage of I, II, III, or IV

94
Q

paraneoplastic syndrome

A

systemic syndromes due to non-hormonal (hypercoagulability, cytokines, etc.) or hormonal effects of a tumor; examples include Cushing syndrome, hypercalcemia, nonbacterial thrombotic endocarditis, and carcinoid syndrome

95
Q

Ewing sarcoma

A

cancer of bone or soft tissue; common in adolescents and young adults; caused by translocation between chromosomes 11 (FLI1 gene) and 22 (EWS gene); Dx via histology, immunohistochemistry, molecular cytogenetics

96
Q

Kaposi sarcoma

A

associated with HIV+ individuals; involves interaction between human herpes virus 8 (HHV-8), inflammatory cytokines, and angiogenic factors in the context of profound immune suppression

97
Q

lucentis

A

angi-VEGF drug that, when injected directly into the vitreous humor of the eye, antagonizes VEGF and not only blocks wet AMD progression but also restores lost vision and reduces vascularity

98
Q

macugen

A

angi-VEGF drug that, when injected directly into the vitreous humor of the eye, antagonizes VEGF and not only blocks wet AMD progression but also restores lost vision and reduces vascularity

99
Q

tip cell

A

specialized highly-polarized endothelial cell that begins process of angiogenesis; resembles a sprouting axon, has many filopodia that sense the surrounding environment; induced by VEGF-A signaling/VEGFR2 on filopodia, receives low notch signal, upregulates Kdr, Nrp, and Flt4; forms through loosening cell junctions (VE-cadherin), matrix remodeling (MMPs), angiogenic factors (VEGF, FGFs, ANG-2, cheekiness

100
Q

stalk cell

A

endothelial cells that work in concert with a single tip cell to promote angiogenesis; differentiate in response to VEGF-A/VEGFR1 and receiving notch signaling, repress Kdr, Nrp, and Flt4 while expressing sFlt1; proliferate when stimulated with VEGF-A, establish firm adherens junctions, deposit basement membrane, express axon-guidance genes (Robo4, Jag1, Flt1)

101
Q

notch

A

family of membrane-bound receptors that are stimulated by membrane-bound ligands (cell contact-dependent signaling); signaling involves internalization of the extracellular domain of notch into the signal-sending cell followed by cleavage of the intracellular domain by the signal-receiving cell, which alters gene expression in the signal-receiving cell; during angiogenesis, endothelial cell stimulation by VEGFA stimulates expression of the notch ligand DII4, which allows bilateral notch signaling/competition for tip cell differentiation; ultimately the tip cell expresses VEGFR2 and becomes the signal-sending cell for notch, while the stalk cells express VEGFR1 and become the signal-receiving cells for notch signaling

102
Q

wet AMD

A

disease of pathologic angiogenesis taking place in the retina, leading to degenerative disease and vision loss

103
Q

c-Abl gene

A

found on chromosome 9, codes for non-receptor tyrosine kinase; constitutively active when translocated to BCR locus on chromosome 22 (t(9;22) Philadelphia chromosome), common in CML and ALL, treatable with imatinib

104
Q

proto-oncogene

A

a normal gene with tightly-regulated expression that usually regulates cell growth; may encode genes such as growth factors, growth factor receptors, signal transducers, transcription factors, or cell cycle regulators; gain-of-function mutations may cause transformation into an oncogene

105
Q

oncogenic viruses

A

viruses that directly induce malignant phenotypes, either through viral genomic integration (leads to over-expression of viral proteins that affect cell growth or disruption of a proto-oncogene) or stimulation of host inflammatory responses with subsequent regeneration (i.e., hepatitis B/C, H. pylori, etc.); examples include EBV (LMP1 oncoprotein stimulates JAK2/STAT pathway and activates Bcl-2, EBNA2 stimulates cyclin D1)

106
Q

initiator

A

a chemical that causes permanent DNA mutations (may be direct or indirect); mutations only truly permanent if they are propagated (i.e., not repaired before the cell divides)

107
Q

promotor

A

a nontumorigenic chemical that reversibly enhances the proliferation of mutated cells; i.e., phorbol esters, hormones, phenols, bile salts, alcohol

108
Q

HIF-1alpha

A

transcription factor that, under hypoxic conditions, drives expression of angiogenic and proliferative genes; under normoxic conditions, it is hydroxylated by prolyl-hydroxylase and targeted for ubiquitinization by VHL

109
Q

VHL protein

A

von Hippel-Lindau protein; under normoxic conditions, targets HIF-1alpha for destruction to prevent pathogenic angiogenesis

110
Q

Von Hippel-Lindau disease

A

inherited loss-of-function mutation in VHL gene, causes increased frequency of hemangioblastomas in the retina and CNS

111
Q

cancer treatments

A

multi-modal: surgery, radiation, chemotherapy

112
Q

cancer chemotherapy

A

drugs used as one part of cancer treatment that are intended to kill all tumor cells, spare normal cells, and increase the host capacity to fight cancer; ideal drugs are nontoxic to normal cells, kill all tumor cells, have a broad spectrum of activity, good distribution in the body, adequate half-life, non-immunogenic, low incidence of side effects, low cost, oral dosing

113
Q

principles of cancer chemotherapy

A

aim for 2-log kill and 4-12 cycles of therapy; constant dose of drug kills a constant fraction of tumor cells; tumor size correlates to duration of therapy, NOT dose

114
Q

cell cycle

A

time required for one cell to become two cells

115
Q

oncogenes

A

mutated proto-oncogenes with dysregulated, autonomous function/constitutive expression that cause unregulated cell proliferation; usually require gain-of-function mutation on only one allele (dominant)

116
Q

MYC oncogene

A

master regulator transcription factor for cell growth found on chromosome 8 that induces expression of cyclin D, rRNA genes, metabolic reprogramming/Warburg effect, and telomerase; can also reprogram somatic cells into pluripotent stem cells; also inhibits growth-suppressing genes, such as CDKI; when translocated to IG gene locus on chromosome 14 (Ig heavy chain promotor) induces Burkitt’s lymphoma

117
Q

cyclins/cyclin-dependent kinases

A

cell cycle regulatory proteins; cyclins are transiently-expressed, unstable proteins that activate CDKs, while CDKs are constitutively-expressed enzymes that phosphorylate target proteins

118
Q

cyclin D1

A

activated by CDK4, phosphorylates RB to allow the cell to pass through the G1 restriction checkpoint; when fused to IgH gene due to d(11;14) causes mantle cell lymphoma; also in plasma cell myeloma and hairy cell leukemias

119
Q

APC/beta-catenin

A

APC normally sequesters and mediates destruction/down-regulation of beta-catenin, which is a transcription factor for various growth factors; loss-of-function mutations in APC lead to beta-catenin accumulation and complexing with TCF, which leads to transcription and unregulated cell growth; causes familial adenomatous polyposis (FAP), requires prophylactic colectomy (affects colon more than other organs)

120
Q

p53

A

tumor-suppressor gene; “guardian of the genome;” senses cellular stress, such as anoxia, DNA damage, oncoprotein activity, and directs cells to enter repair, senescence, or apoptosis; mediators include p21, GADD45, and BAX; regulated by Mdm2, which ordinarily promotes ubiquitinization of p53, but cellular stress induces phosphorylation of Mdm2/liberation of p53, which is subsequently acetylated (by ATM/ATR family) and acts as a transcription factor

121
Q

Bcl-2

A

protein that antagonizes apoptosis/stabilizes mitochondrial membrane to prevent cytochrome c leakage; neutralized by BH3; overexpressed in many lymphomas, particularly follicular lymphoma (lack of normal apoptosis in germinal center)

122
Q

BAX

A

p53 mediator, induces cells to enter apoptosis

123
Q

direct-acting carcinogens

A

highly reactive electron-deificent compounds that react with electron-rich sites (such as DNA, RNA, protein, etc.) and do not require enzymatic processing, i.e. alkylating agents

124
Q

indirect-acting carcinogens

A

compounds that require metabolism by CYP450 systems to become carcinogenic

125
Q

tumor suppressor genes

A

genes that control cell growth; loss-of-function recessive mutations lead to mutator phenotypes/cancer

126
Q

anti-apoptosis genes

A

apoptosis-inhibiting genes; includes Bcl-2, IAP

127
Q

apoptosis genes

A

apoptosis-promoting genes; includes Fas (CD95)/FasL, FLICE death complex, procaspase 8/3, cytochrome c, BAX/BAK, APAF-1, BH3

128
Q

ERB B2 gene (Her2/Neu)

A

often upregulated in breast carcinomas, poor prognostic sign (predicts lack of responsiveness to estrogen therapy); treatable with trastuzumab, an anti-Her2 mAb

129
Q

c-KIT gene

A

mutation common in gastrointestinal stream tumors; codes for receptor tyrosine kinase, mutation causes upregulation; treatable with imatinib (Gleevec)

130
Q

RAS oncogene

A

pro-growth signal transducing protein, mutated oncogene is constitutively active and does not require receptor stimulation; mutations commonly affect GTP binding or GTP hydrolysis

131
Q

NPM1

A

most commonly-mutated gene in AML (30% of cases); good prognostic indicator, typically includes a 4bp insertion

132
Q

BRAF oncogene

A

codes for serine/threonine protein kinase, mutations found in all hairy cell leukemia, also common in colon cancer, melanomas, and benign nevi; treatable with vemurafenib and dabrafenib

133
Q

PIK3 oncogene

A

codes for lipid kinase, mutations in the catalytic subunit lead to increased enzyme activity and are found in various cancer; PI3K is negatively regulated by PTEN

134
Q

CDKN2A

A

encodes p16 and ARF; inhibits Cyclin D/CDK4 complex, promotes RB-mediated cell cycle inhibition

135
Q

Li-Fraumeni syndrome

A

inherited p53 mutation, endows a risk of developing cancer by 50 y.o. that is 25X higher than average; characterized by a wide variety of cancers at younger ages and multiple cancers in the same individual

136
Q

Lynch syndrome

A

caused by mutations in mismatch repair genes, induces a mutator phenotype and micro satellite instability; individuals have much higher risk of cancer

137
Q

axon guidance gene families

A

gene families that have at least one receptor and one ligand in both neural and vascular tissue; includes Netrin, Sema3, Slit, and Ephrin

FPP/MSS (5 decks)

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