Term
| Skipper-Schabel Cancer Model |
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Definition
| Linear Growth. Applicable to the description of early stage cancers/tumors. Doubling time is constant as well as the lethal drug dose per cell. Assumptions of homogeneity of cancer cells w/o growth restrictions (before angiogenic switch). Good for modeling leukemia, lymphoma, & rapidly metastasizing tumors. Best treatment window but disease usually asymptomatic at this point and often missed by clinicians. |
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Term
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Definition
| Non-Linear Growth. Large tumors consisting of proliferating and non-proliferating cells. Sub-optimal growing conditions for cells w/ heterogeneity amongst cells. *Increasing the dose may not improve activity. Treat minimal disease is more effective. Use small & frequent dosing.* |
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Term
| Chemo Drug Dosing & Scheduling |
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Definition
| Individually dosed based on patient's body surface area (BSA). Admin. maximum tolerated doses. Must monitor closely: Very small therapeutic index highly variable depending on physical condition, age, prior treatment, genetics, other med. problems, etc. Allow rest periods between treatments in order to rescue normal tissues. **Rescue periods also allow cancer to regrow!! |
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Term
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Definition
| Slow progression of rapidly dividing cells through the cell cycle and/or utlize the rapid proliferation of cancer cells to incorporate lethal doses of toxic compounds into the cancer cell. CDK inhibitors, antimetabolites, & nonspecific drugs. |
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Term
| Mechanisms of Cancer Resistance |
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Definition
1. Decreased drug uptake.
2. Increased drug transport out of cell.
3. Mod. of targets.
4. Increased detox. of drugs.
5. Increased DNA Repair.
6. Decreased apoptosis. |
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Term
| 1. Drug Uptake Resistance |
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Definition
| Most problematic for drugs utilizing transport proteins to enter the cell. Lesser extentent endocytotic methods. Diffusion of lipid-soluble drugs least effected by this mechanism of resistance. |
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Term
| 2. Increased Transport out of cell Resistance |
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Definition
| Energy dependent transport of drugs out of cells mediated by ATP-binding cassette (ABC) proteins including P-glycoprotein (P-gp) and Multidrug Resistance Associated Protein (MRP). Non-specifically transport large, hydrophobic compounds out of cells. DOES NOT affect small molecule-type drugs (antimetabolites, alkylating agents, & platinating agents). |
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Term
| 3. Mod. of Targets Resistance |
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Definition
| Overexpression, Underexpression, Use of Alternative pathway, Decreased Binding Affinity, Etc. Effects all classes of drugs but slow to develop. |
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Term
| 4. Increased Detox Mechanism |
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Definition
| Increased glutathione conjugation via glutathione-S-transferases (GST)due to upregulation. Addition mechanisms. Affects all drug groups. |
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Term
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Definition
| Upregulation of DNA repair mechanisms to correct damage inflicted upon cancer cell DNA by DNA alkylating drugs. |
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Term
| 6. Decreased Apoptosis Resistance |
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Definition
| Increased expression of oncogenes and/or Decreased expression of apoptotic genes. Counter to DNA alkylating drugs. |
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Term
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Definition
| Resistance Development Model. "The Possibility of developing drug resistance to two or more drugs is lower than to only one drug." Combine drugs with different working mechanism with non-overlapping toxicity and non-cross resistance mechanisms. |
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Term
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Definition
-Nausea/Vomiting: Direct activation of chemo-receptors in the brain.
-Liver/kidney toxicity. Monitor Closely.
-Cell Death in normal, rapidly reproducing cells in the GI tract (Diarrhea), hair follicles (Alopecia), and bone marrow (Myelosuppression).
-**Tumor Lysis Syndrome** |
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Term
| Tumor Lysis Syndrome Symptoms |
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Definition
Caused by the rapid death of cancer cells following chemotherapy.
-Hyperkalemia
-Hyperphosphatemia
-Hyperuricemia (prophylactic Allopurinol)
-Hypocalcemia
-(Possible Cytokine Storm) |
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Term
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Definition
-Peripheral Neuropahty
-Cardiotoxicity/Cardiomyopahty
-Chemo Brain: Long term memory & cognitive difficulties due to loss of neuronal stem cells of oligodendrocytes causing demyelination.
-Secondary Cancer (genotoxicity) |
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Term
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Definition
| Pain- Stresses the body, inhibits immune system, increases mortality. Treat w/ narcotics. |
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Term
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Definition
| Treat with Serotonin Receptor Antagonists Ondansetron or Granisetron and/or Dopamine Receptor Antagonist Metoclopramide. |
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Term
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Definition
| Numerous treatments. Pharma approach, group support, involvment, animal therapy, etc. Depressed patients have much poorer outcome. |
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Term
| Vaccines in Cancer Prevention |
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Definition
| Example: 1)HPV-Gardasil. Protects against infection with transforming, high-risk HPV variants 6, 11, 16, & 18. 2. Hepatitis B virus & liver cancer. Research into prevention of liver cancer (Hepatitis B & C) & certain hemological cancers (Epstein-Barr). |
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Term
| Active Cellular Immunotherapy |
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Definition
Individualized treatment strategy.
Ex. Sipuleucel-T (Provenge): Harvest APCs from patient, present them w/ Prostate Specific Antigen & grwoth factors, reinfuse into patient, and then allow activated APAs to generate a T-cell response against Hormone-Refractory Prostate Cancer (HRPC)cells. |
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Term
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Definition
Covalent binding of alkyl groups onto DNA, RNA, & Proteins. Mono or di functional. Difunctional can crosslink. Non-specific class.
Side FX: bone marrow suppression, GI irritation, nausea/vomiting, alopecia, gonadal dysfunction, infertility, mutagenic/carcinogenic. Resistance developed via increased DNA repair, detox, & decreased apoptosis.
1. Mechlorethamine
2. Cyclophosphamide/2-mercaptoethane
3. Chlorambucil
4. Carmustine
5. Streptozocin
6. Cisplatin |
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Term
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Definition
| Nitrogen Mustard: Potent difunctional alkylator/crosslinker. Risk of extravasation injury. Used formerly in Hodgkin's lymphoma. |
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Term
| Cyclophosphamide/2-Mercaptoethane |
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Definition
| Nitrogen mustard. Potent alkylator & crosslinker. Most commonly utlized chemo drug. Pro-drug requiring activation through P450 system so no extravasation injury risk. Bladder & renal toxicity due to toxic metabolite acrolein. Prevent toxicity via hydration & 2-mercaptoethane (Mesna) which neutralizes acrolein & enhances secretion. |
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Term
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Definition
| Difunctional nitrosourea alkylator & crosslinker. Good CNS penetration. Indicated for primary brain tumor, lymphoma, & multiple myeloma. |
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Term
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Definition
| Nitrosourea monofunctional glucose derivative. Accumulates in liver, kidney, & pancreas. Destroys pancreatic beta-cells. Indicated in endocrine pancreatic cancer. |
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Term
| Cisplatin/Carboplatin/Oxaliplatin |
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Definition
DNA crosslinker.
Acute Tox: hypersensitivity, nausea/vomiting.
Subacute Tox: renal, gonadal tox. w/ mild myelosuppression.
Chronic Tox: peripheral & central neurotoxicity, acoustic nerve damage, vascular toxicity. |
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Term
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Definition
DNA Intercalators, Single Strand Breakers, and Topoisomerase II inhibitors. Cell cyle non-specific. Resistance via efflux pumps, decreases topoII affinity, increased topoII expression, increased DNA repair, and increased GST detox.
1. Actinomycin D
2. Mitomycin C
3. Bleomycin
4. Anthracyclines (Doxorubicin/Daunorubicin)
5 |
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Term
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Definition
Intercalates DNA/RNA & TopoII inhibitor.
Myelosuppression, extravasation injury risk, & increased sensitivity to radiation (avoid sun). |
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Term
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Definition
Requires liver activation. DNA crosslinker, generates loads of damaging free radicals that damage DNA.
Risk of delayed myelosuppression, kidney damage, & lung fibrosis. |
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Term
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Definition
| DNA intercalator, DNA strand breaker, & Free Radical formation. Hypersensitivity rxns, skin hyperpigmentation, lung tox (pulmonary fibrosis). ONLY MILD MYELOSUPPRESSION-Used in many chemo drug combos. Indicated in testicular cancer. |
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Term
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Definition
TopoII/helicase inbitors, strand breaker, intercalator, & free radical former. Liver metabolism. Extravasation injury, severe myelosuppression, severe cardiac toxicity.
Doxorubicin- Broad spectrum/breast cancer.
Daunorubicin- Acute leukemias. |
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Term
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Definition
Mimic Naturally Occurring Compounds. Interfere with DNA/RNA & Protein Synthesis. S-phase selective.
1. Methotrexate
2. Mercaptopurine
3. 5-Fluorouracil
4. Capecitabine/Gemcitabine |
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Term
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Definition
| Folic acid analogue. Inhibites dihydrofolate reductase thereby preventing synthesis of purines, pyrimidines, and methionine. Side FX: myelosuppression, renal tox at high dose, & liver tox chronic use. |
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Term
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Definition
| Folinic Acid. Compound used to rescue normal cells. Antidote to methotrexate. Utlizes side pathway. |
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Term
| 5-Fluorouracil/Capecitabine |
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Definition
Pyrimidine analogue. Transformed into cytotoxic metabolites/false nucleotides. Inhibites thymidylate synthase. Folinic acid enhances effects of 5-FU. Side FX: myelosuppression, GI tox., photosensitivity, chemobrain.
**Must check if patient is dihyropyrimidine dehydrogenase (DPD) deficiency. Can be fatal.**
Indicated in colorectal cancers & combination therapy. |
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Term
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Definition
Purine analogue. False nucleotides incorporated into DNA/RNA. Widely used in acute/chronic leukemias & combination therapy. Side FX: myelosuppression, liver toxicity.
**Increased tox if patients have deficiency in thiopurine-S-methyltransferase.** Also, do not mix w/ allopurinol. |
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Term
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Definition
Large, complex, & cycle specific. Resistance due to efflux pumps & mutations in targets. Microtubule formation inhibitors & topoisomerase inhibitors.
1. Vinca Alkaloids- Vincristine/Vinblastine.
2. Taxanes- Paclitaxel/Docetaxel
3. Podophyllotoxin- Etoposide/Teniposide
4. Camptothecins- Topotecan/Irinotecan |
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Term
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Definition
Inhibits microtubule formation. Block cells in G2 & M phase. Resistance by increased tubulin synthesis & efflux pumps. Risk of extravasation injury. Intrathecal accident=instant death.
Vincrestine: non-Hodgkin lymphoma, pediatric solid tumors, disseminated cancers. Neurotox w/ little myelosuppression.
Vinblastine: Testicular carcinoma, non-hodgkin lymphoma. |
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Term
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Definition
Inhibition of microtubule depolymerization. Stabilizes microtubules resulting in formation of abnormal microtubule bundles. Blocks cells in G2-M transition. Side FX: Hypersensitivity, peripheral neuropahty, mucositis, w/ ulceration in mouth & throat. Broad spectrum.
Paclitaxel (Taxol)
Docetaxel |
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Term
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Definition
Inhibitors of topoII. S-G2 phase specific. Resistance through mod. of TopoII, increased topoII expression, and efflux pumps. Myelosuppression common. Indicated in SCLC & testicular cancer.
Etoposide/Teniposide |
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Term
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Definition
TopoI inhibitor. **Contraindicated in paitents w/ Gilbert's disease. Indicated in colorectal cancer w/ 5FU.
Irinotecan |
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Term
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Definition
Anti-inflammatory & immunosuppressants.
Induce lymphocyte apoptosis & prevent immune cell proliferation. Indicated in lymphoma/leukemia. May reduce the cardiotoxicity of doxorubicin. Adrenal atrophy, immunosuppression, HTN, edema, heart insufficiency.
1. Dexamethasone
2. Prednisone
3. Prednisolone
**Counter Indications: Cushing Syndrome, Cardiac Disease, Diabetes, Osteoporosis. |
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Term
| Monoclonal Antiboides (MAB) |
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Definition
1. Elimination of Cancer through complement-mediated cytotoxicity.
2. Labeling w/ cytotoxin or radioactive molecule.
3. Blockade of receptor binding sites to prevent activation.
4. Binding and inhibition of receptor activators.
Part of combination therapies. Allergic reactions only major side effect.
Trastuzumab (HER/Neu)
Rituximab/Ibritumomab (CD20)
Cetuximab (EGFR)
Panitumumab (EGFR)
Bevacizumab (VEGF) |
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Term
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Definition
| Target: HER/Neu Breast Cancer. Binds to Human epidermal growth factor recptor 2 (HER2). Used in metastatic breast cancer. Kills cells by complement mediated lysis and blockage of signal transductions. Side FX: Cardiotoxicity w/ enhanced toxicity of anthracyclines & cyclophosphamide. |
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Term
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Definition
| Binds human epidermal growth factor 1 (HER1). Used to treat metastatic colorectal cancer in patients w/ wildtype KRAS & squamous cell carcinoma of head/neck. Side FX: Skin reactions, rare lung fibrosis,& deadly to fetuses. |
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Term
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Definition
| Binds CD20 to induce complement toxicity. Used to treat low grade non-Hodgkin's lymphoma, other combos. Side FX: Moderate allergic rxns, rare fatality following infusion. |
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Term
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Definition
| Targets CD20 on B-cells. Chelated w/ radioactive yttrium/indium. AB is a homing missil shuttling radiation directly to cancer cells. Used in follicular B-cell non-Hodgkin's lymphoma. Side FX: Radiation exposure. |
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Term
| Imatinib mesylate (Gleevec) |
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Definition
| Inhibits receptor tyrosine kinases RTK for PDGF, BCR-ABL yrosine kinase and c-kit. Indicated Chronic myeloid leukemai & gastrointestinal stromal tumors. Side FX: edema/fluid retention, neutropenia, thrombocytopenia, liver tox, renal tox, & pregnancy risk. |
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Term
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Definition
| TK-Inhibitor. Multiple RTKs. Indicated for renal cell carcinoma, gastrointestinal stromal tumors, & other solid tumors. Side FX: minor-fatigue, diarrhea, nausea, anorexia, HTN, skin discoloration, hand-foot reaction & stomatitis. |
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Term
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Definition
| Inhibitors of EGF receptor's tyrosine kinase domain. Increases survival time in some patients. Not that effective. Side FX: Asthenia, Bleeding. |
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Term
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Definition
| Inhibitors of EGF receptor's tyrosine kinase domain. Increases survival time in some patients. Not that effective. Side FX: Asthenia, Bleeding. |
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Term
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Definition
| Proteasome Inhibitor. Blockage results in build up in proteinacous waste. Cell cycle arrests, apoptosis occurs, angiogenesis is blocked, & tumor growth is delayed w/ enhanced susceptibility to other chemo drugs. Indicated in multiple myeloma & mantel cell lymphoma. Side FX: asthenia, peripheral neuropathy, myelosuppression, shingles. |
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Term
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Definition
| AB targeting vascular endothelial growth factor (VEGF). Prevents angiogenesis. Numerous indications w/ relatively few side fx. |
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Term
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Definition
| Direct anti-tumor act., immune modulation, & anti-angiogenic activity. Used to treat multiple myeloma. Black Box Warning for blood clotting requiring prophylaxtic treatment. Constipation, fatigue, birth defects, neuropathology, etc. |
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