Exam 4 (Donnelly) Flashcards by Melanie Walukonis

What phase of the cell cycle are most cells in?

G0 (turned on by GFs/inflammation)

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What push the cell cycle forward?

proto-oncogenes (normal genes that turn on cycle)

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If genes are more functional or mutated, they become ____.

oncogenes

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What stops/slows cell cycle?

tumor suppressor genes

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What is KIT?

common mutation of oncogenes that leads to mast cell tumor

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What are the 6 hallmarks of cancer?

sustain proliferative signaling
evade growth suppressors
activate invasion / metastasis
enable replicative immortality
induce angiogenesis
resist cell death

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Which cancer hallmark is the most fundamental?

Sustain proliferative signaling

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Two barriers to cancer having immortality?

senescence (being in irreversible, non-proliferative state of G0)
crisis (cell death)

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How does cancer avoid cell death (crisis)?

autophagy (eats itself)

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Some cancers can add _____ using _____ (enzyme) to lengthen and divide longer than a normal cell.

Telomeres
Telomerase

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Angiogenic switch

point where vasculature sprouts new vessels toward cancer

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What is the promoter of angiogenesis?

VEGF (vascular endothelial growth factor)

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What is an inhibitor of angiogenesis?

TSP

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Epithelial-Mesenchymal Transitions (EMTs)

cancer figures out how to move away from other cells and survive somewhere else

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Therapy directed at antigen/molecule specific to tissue is _____

Targeted therapy

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What are two targets for targeted therapy of cancer?

Tumor Associate Antigens
Tumor Specific Antigens

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Tumor Associated Antigens

tumor overexpresses proteins on cell surface (still in normal cells)

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Tumor Specific Antigens

tumor cell has specific antigens (NOT in normal cell)

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Monoclonal antibodies

every antibody finds same antigen (same binding site)

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Antibody

protein that seeks out antigens

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Drugs that end in ____ are monocloncal antibodies

Mab

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3 Mechanisms for Monoclonal Antibodies as Targeted Cancer Therapy

antibody-dependent cell cytotoxicity
compliment-directed cytotoxicity
3 stim apoptosis directly

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Antibody-dependent cell cytotoxicity

NK (natural killer) cell binds to antibody
= stimulated & kills B cell

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Compliment directed cytotoxicity

antibodies stimulate cascade –> hole/leaky B cell

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CD20

antigen/protein on surface of B cells

What is the example of CD20 directed monoclonal antibody targeted therapy?

Rituximab

What does Rituximab treat?

B cell lymphomas

What is the function of CD20?

B cell activation | proliferation/differentiation of B cells

Function of CD52

unknown cell surface glycoprotein

Drug which targets CD52 in humans

Alemtuzumab

Where is CD52 located?

B & T cells | monocytes | dendritic cells | sperm (NOT specific)

What do small molecule drugs end in?

Toceranib (Palladia) blocks which receptors? (and therefore blocking cell growth?)

KIT | PDGFRB (receptor tyrosine kinases)

What does Toceranib (Palladia) treat?

MCT in dogs

Two drugs that are small molecule inhibitors

Toceranib (Palladia) Imatinib (Gleevec)

What receptors are blocked by Gleevec (Imatinib)?

KIT | PDGFRA/B

What does (Imatinib) treat?

chronic leukemia

What growth factor is secreted by tumor cells for angiogenesis?

VEGF

What is the function of Bevacizumab (Avastin)?

bind/destroy VEGF so it can't bing to VEGFR = stops angiogenesis

What is the function of Bevacizumab (Avastin)?

bind/destroy VEGF so it can't bind to VEGFR = stops angiogenesis

What does EGFR do (epidermal growth factor receptor)?

dimerization --> cell division

EGFR = _____

HER

What drug bind & inhibits EGFR/HER?

Trastuzumab (Herceptin)

Antibody Drug Conjugates (ADC)

put toxic chemical on antibody so toxic drug kills cell

Radioimmunoconjugates (RIC)

deliver radioactive substance to kill cancer directly

What are two targeted radionucleotides for cancer treatment?

quadramet iodine

Using Quadramet, _____ is taken up by active bone and kills cancer.

phosphorus

Iodine (radionucleotide treatment) treated what type of cancer?

thyroid cancer

BBR2 upregulated in _____ cancer, using radio_____.

prostate radiopeptides

Local Disease

expand/destroy in certain area (NOT other locations)

Systemic Disease

commonly in multiple places

What is primary treatment of local disease?

surgery

What is primary treatment of systemic disease?

chemotherapy

Chemotherapy

treatment of disease w/ chemicals

What is a cytotoxic drug?

toxic to inside of cell | causes DNA damage

Maximum Tolerated Dose (MTD)

highest dose that can be given without irreversible/unacceptable side effects

Metronomic

giving a low dose of chemo over long period time

(T/F) Metronomic chemotherapy is cytotoxic.

Cells with _______ are most susceptible for cytotoxicity.

euchromatin (rapidly dividing cells)

Gompertzian Growth Kinetics

demonstrates how cancer happens and progresses

Angiogenic switch

threshold where cancer cell needs blood supply for continuous rapid growth

Where is cancer most susceptible to chemo?

between angiogenic switch and above

Threshold for Clinical Detection

part of gompertzian growth kinetics curve at plateau phase cell growth falls, nutrient supply lacks, hard to grow at same rate due to its size

What are the 3 types of rapidly dividing cells that are most affected by chemotherapy?

Bone Marrow Hair Follicle Cells GI cells

What occurs due to bone marrow cell destruction by chemotherapy?

myelosuppression (low white cell count)

What occurs due to hair follicle cells being destroyed by chemo?

alopecia

What occurs due to GI cells being affected by chemo?

V+ / D+

Chemo is (specific/nonspecific) to cell type.

nonspecific

What is the term for lowest WBC count after chemo?

Nadir

When is lowest WBC count seen after chemo?

7 days post-chemo

When is GI injury/signs seen after chemo?

3-5 days post-chemo

Mechanism for Alkylating Agents (chemo)

alkyl adducts (sticky parts) to DNA prevent DNA replication/transcription

What cell cycle are alkylating agents affecting?

non-specific | can affect any stage

What two drugs are within alkylating agent class of chemo?

Cyclophosphamide Lomustine

What cancer do alkylating agents treat primarily?

lymphoma

Cyclophosphamide side effect

sterile hemorrhagic cystitis

Lomustine side effect

hepatotoxicity (liver)

Antimetabolites chemo mechanism

fake DNA bases inhibit DNA base production --> prevent DNA replication

What cell cycle phase is inhibited by antimetabolites?

S phase

What are the 3 drugs within antimetabolites (chemo)?

5-FU Cytosine Arabinoside Rabacfosadine

5-FU side effect

fatal neurotoxicity in cats

What is specific about cytosine arabinoside?

crosses blood-brain barrier

What does cytosine arabinoside treat?

CNS tumors

What does Rabacfosadine treat?

lymphoma

Side effect of Rabacfosadine

fatal pulmonary fibrosis

Topoisomerase inhibitors (chemotherapy class) mechanism

DNA cannot unwind | generate free radicals which damage DNA

What is the main drug within the topoisomerase inhibitor class?

Doxorubicin

What are the two side effects of doxorubicin

cardiotoxicity | nephrotoxicity in cats

What does doxorubicin treat?

any bad "omas" lymphoma, sarcoma, carcinoma

Anti-microtubule chemo class (vinca alkaloids) mechanism

inhibit microtubule assembly = death

Side effects of vinca alkaloids (anti-microtubule chemo)

neuropathy & blistering

What are the 2 main drugs that are anti-microtubules?

Vincristine Vinblastine

What does vincristine treat

lymphoma

What does vinblastine treat

blasts masts! (MCT)

Platinums / Cross-linking Agents (chemotherapy class) mechanism

DNA cross-linking (difficult to replicate)

What are the two drugs that are platinums?

Cisplatin Carboplatin

What does cisplatin treat?

carcinoma/sarcoma

What is the side effect to cisplatin in dogs?

nephrotoxicity

What is the side effect of cisplatin in cats?

SPLATS cats = fatal pulmonary edema

Carboplatin treats

osteosarcoma

L-asparaginase mechanism

enzyme that cleaves asparagine --> aspartic acid cancer cells cannot make own asparagine unlike normal cells

What is a side effect of L-asparaginase over time?

anaphylactic reaction

Signal Transduction Inhibitors (tyrosine kinase inhibitors) mechanism

block cell signaling surface receptors (KIT, VEGF, PDGF)

What is the main drug that is a tyrosine kinase inhibitor?

TKIs (toceranib or palladia)

What does toceranib (palladia) treat?

MCT