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52 Cards in this Set
- Front
- Back
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What is chemoprevention?
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the use of specific natural or synthetic agents to reverse, suppress, or prevent the carcinogenic process, thereby preventing the development of clinically evident cancer
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In terms of cancer prevention, who are considered "Primary" populations?
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a general population of healthy individuals at risk
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In terms of cancer prevention, who are considered "secondary" populations?
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individuals with premalignant lesions to prevent the progression of cancer
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In terms of cancer prevention, who are considered "tertiary" populations?
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prevention of a second primary cancer
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What is LCIS?
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lobular carcinoma in situ
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What patient population is tamoxifen approved for cancer prevention?
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tamoxifen is FDA approved for risk reduction of breast cancer in those at high risk or with ductal carsinoma in situ (DCIS), for both pre- and post-menopausal; 20mg QD x 5 years
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What is EMT in cancer cell progression?
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tumor border cells undergo epithelial-mesenchymal transition to gain characteristics of normal mesenchymal cells (protease secretion) and lose characteristics of normal epithelial cells (adhesiveness).
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What process occurs once cancer cells migrate to other areas of the body in order to form additional tumor masses?
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once cancerous cells arrive at a new location, they undergo MET (mesanchymal-epithelial transition) to become more epithelial-like as they grow into a new tumor at another body site. This tumor will usually be recognizable as having been derived from the original primary tumor, but will be more advanced (and cellularly heterogeneous and thus harder to kill) than the primary tumors. Platelets aggregate around tumor cells in the circulation and protect them as a physical barrier from being killed. The platelets also secrete factors that enhance tumor cell survival
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What are some of the systemic effects of cancer?
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cancer can cause an increase in clotting tendency from dysregulation of clotting; depleted WBC's (particularly neutropenia) resulting in increased infections; cachexia and sepsis-like condition caused by increased TNFalpha released by tumor cells
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How do cancer cells effect immune system response (particularly cell surface antigen proteins)?
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cancer cells shed (gets rid of) these antigens and also inactivate the immune system. Cancer cells inhibit the ability of antigen presenting cells (eg, dendritic cells) to present antigen and induce populations of immune cells that actually suppress immunity
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Which phase of the cell cycle do most cancer drugs work on?
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most cancer agents have activity against cells in division process/proliferation, this is the S-phase of cell division and proliferation (this is where DNA synthesis takes place)
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What agents are included in the alkalyting agent class of ant-cancer drugs?
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nitrogen mustards, nitrosourea, alkyl sulfonate, triazenes, and platinum compounds are all considered alkalyting agents
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What are the two classes of alkalyting agents for how they effect DNA?
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intrinsically reactive agents- active by itself or direct acting (Mechlorethamine, Carmustine, Busulfan, Chlorambucil, Cisplatin, Carboplatin, oxaliplatin); Require Metabolic Activation to alkylating species (Cyclophosphamide)
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What is the general MOA of the alkalyting agents?
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Crosslinking of DNA, and Alkylation (or carbamoylation) of DNA and/or protein; This reaction leads to formation of covalent bond by alkylation of nucleophilic moieties; Overall result of these agents is DNA damage, resulting in death by apoptosis
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How does cyclophosphamide work?
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cyclophosphamide goes through CYP 450 activation, the acyclic tautomer aldosphosphamide then undergoes nonenzymatic spontaneous cleavage into phophoramide mustard (the active metabolite used for anti-cancer activity)
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What is generally the mechanism of resistance cancer generally forms to alkylating agents?
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the primary mechanism of resistance cancer is the increased activity of DNA repair enzymes
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What is the order of hormone formation/release involving endocrine hormones?
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start in hypothalmus by releasing LHRH, then to pituitary, releasing gonadotropins (FSH and LH), then to the testes to produce testosterone or the ovaries to produce estrogen and progesterone; the final hormones provide feedback stimulation to the hypothalmus to start the cycle over again.
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How do antiestrogen drugs work?
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antiestrogen agents inhibit the effect of estrogen by binding to estrogen receptors (competitive inhibitors), which prevents transcription and binding of other important cofactors
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What are the antiestrogen agents used for targeted cancer therapy?
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tamoxifen, toremifene, and fulvestrant; tamoxifen and toremifene are both absorbed orally, while fulvestrant is administered IM; all are highly protein bound and extensively CYP 450 metabolized
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What are indications and significant SE's of antiestrogen therapy?
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antiestrogens are indicted for treatment of breast and endometrial cancer; most significant SE's include hot flashes and thromboembolic events
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What are positive and negative estrogen like SE's of tamoxifen?
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benefits include decrease risk of breast cancer, lowers LDL's, and strengthens bones; negative includes increasing uterine cancer risk and increasing blood clot risk
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How do aromatase inhibitors work (MOA)?
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aromatase inhibitors prevent formation of estrogen by preventing the action of aromatase, which makes estrogen from androgens located within fat cells (therefore decreasing the amount of estrogen in the body)
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Of the aromatase inhibitors, which work with competitive inhibition and which have irreversible inhibition?
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anastrozole and letrozole are both competitive aromatase inhibitors, while exemestane is an irreversible aromatase inhibitor
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Which of the aromatase inhibitors are renally excreted for elimination?
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letrozole is the aromatase inhibitor excreted primarily in the urine
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What is the primary indication for aromatase inhibitors and which population are they best suited for?
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aromatase inhibitors are indicated for breast cancer, and are ideal for postmenopausal women (since their ovaries are not functional)
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What is the MOA of antiandrogen agents?
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antiandrogen agents inhibit testosterone binding to androgen receptors
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What is the primary indication and significant SE's of antiandrogens?
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antiandrogens are indicated in prostate cancer, and all have diarrhea as the primary SE (nilutamide also has a disulfiram-like reaction, so no EtOH); important to monitor LFT's with these drugs
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What is the MOA of LHRH agonists?
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leutenizing hormone releasing hormone agonists initially stimulate gonadotropin synthesis, but chronic use suppresses endogenous gonadotropin synthesis through negative feedback regulation
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What are the LHRH agonist agents and how are they administered?
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leuprolide and goserelin; these agents are administered subcutaneously and excreted renally
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What are the indications and SE's for LHRH agonists?
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primarily indicated in prostate cancer (also may be used in breast cancer); SE's include hot flashes, decreased libido, impotence, gynecomastia, and tumor flare
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What is the MOA of GnRH antagonists (gonadotropin-releasing hormone)?
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GnRH antagonists directly compete with GnRH receptors in the pituitary gland; these have NO tumor flare, but have the potential for life-threatening allergic reactions
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For monoclonal antibodies, what source does "u" identify?
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"u" identifies human monoclonal antibodies
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For monoclonal antibodies, what source does "o" identify?
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"o" identifies mouse monoclonal antibodies
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For monoclonal antibodies, what source does "zu" identify?
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"zu" identifies humanized monoclonal antibodies
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For monoclonal antibodies, what source does "xi" identify?
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"xi" identifies chimeric monoclonal antibodies
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For monoclonal antibodies, what source does "a" identify?
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"a" identifies rat monoclonal antibodies
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What is the difference between the two types of monoclonal antibodies?
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unconjugated (naked) contain only the antibody and have no drug or radioactive material attached; conjugated Mabs are joined to a chemotherapy drug, radioactive particle, or a toxin
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How does rituximab work?
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rituximab is a mAb against CD20 on B-cells which acts by antagonizing growth signaling pathways as well as mediating complement-dependent cell lysis; given IV only; indicated for patients with low grade or follicular CD20 positive B-cell non-Hodgkins lymphoma
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What is the MOA for trastuzumab and what does it target?
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Herceptin (trastuzumab) is a humanized mAb targeting HER2 indicated for breast cancer; it enhances chemotherapy-induced cytotoxicity and antagonizes growth signaling pathways of cancer cells; most significant SE is heart failure
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How are patients qualified for use with trastuzumab?
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first take an immunohistochemistry (IHC): 3+ - predictive of response, 2+ - must perform FISH analysis, 0-1+ - no indication; if FISH analysis performed, positive is predictive of response and negative is no indication
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What is the MOA and target of cetuximab?
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cetuximab is a chimeric mAb against Epidermal Growth Factor Receptor (EGFR, a.k.a. HER1); MOA is to antagonize growth signaling pathway and enhance chemotherapy-induced cytotoxicity
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What are the approved indications for cetuximab?
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cetuximab is approved for colon cancer (alone or in combination with irinotecan) and for head/neck cancer in combination with radiotherapy
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What are SE's of cetuximab?
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cetuximab has potential SE's of acneform rash (good, b/c means it is working), hypomagnesemia, and rare but potentially fatal pulmonary toxicity
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What is panitumumab and what is it's MOA?
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panitumumab is a human mAb against Epidermal Growth Factor Receptor (EGFR); MOA- Antagonize growth signaling pathway and enhance chemotherapy-induced cytotoxicity
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What is the indication for panitumumab and common SE's?
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panitumumab is indicated for colon cancer in metastatic patients who have disease progression on or following 5-FU, oxaliplatin and irinotecan containing chemotherapy regimens; SE's include acneform rash, hypomagnesemia, and rare but fatal pulmonary toxicity
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What is VEGF?
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vascular endothelial growth factor- this is an important signaling protein involved in tumor angiogenesis (stimulates blood vessel growth)
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What is bevacizumab and it's MOA?
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bevacizumab is a humanized mAb to Vascular Endothelial Growth Factor (VEGF); Mechanism of action- Inhibits blood vessel formation
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What are indications and SE's of bevacizumab?
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bevacizumab is indicated for Colon Cancer - in combination with 5-FU based chemotherapy; Lung Cancer - in combination with platinum based chemotherapy; Breast Cancer - in combination with paclitaxel based chemotherapy; SE's include Bleeding, thromboembolism , proteinuria, hypertension, GI perforation
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What is the difference between invasive and non-invasive cancer?
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in situ is non-invasive; invasive is when the cancer gets outside of the original structure making it much more difficult to treat
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What types of cancers have effective screening techniques currently available?
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colorectal, cervical, breast, prostate, skin, testicular, and oral
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What is needed for a diagnosis of cancer?
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a biopsy of some sort is needed to diagnose cancer; treatment generally does not start without a diagnosis or prior to biopsy
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What is the difference between dysplasia and hyperplasia?
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dysplasia involves abnormal cells growing, while hyperplasia involves abnormal or increased growth of cells
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