Term
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Definition
| Unaltered, normal allele of gene that controls cellular growth and differentiation |
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Term
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Definition
Potentially cancer causeing gene
Proto-oncogene that has been altered by a carcinogenic agent |
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Term
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Definition
| Encode proteins that inhibit cell division and trigger apoptosis |
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Term
| What are the 6 hallmarks of Cancer Cells? |
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Definition
1. Self-sufficiency in growth signals
2. Insensitivity to antigrowth signals
3. Tissue Invasion and metastasis
4. Limitless potential for replication
5. Sustained angiogenesis
6. Evading apoptosis |
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Term
| What is the Gompertzian theory of cell growth? |
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Definition
-Follow a non-linear growth curve
-Growth fraction decreases as tumor size increases
-Growth rate is initially rapid, then flattens out
-Growth rate slows due to tumor outgrowing blood and nutrient supply |
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Term
| What assumptions are the Goldie-Coldman Hypthesis based on? |
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Definition
-Tumors have an inherently higher rate vs. normal cells
-With progression, there appears to be a continued increase in mutation rate |
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Term
| What are the Goldie-Coldman Hypothesis? |
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Definition
Mutations randomly result in altered phenotypes that confer cellular resistance to chemotherapeutic drugs
-Probability of resistance cells depends on tumor size. |
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Term
| What types of Mechanisms cause chemotherapeutic failure? |
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Definition
Kinetic Resistance
-Slow-growing, poor vascularization
Pharmacological Resistance
-Pharmacological sanctuary, non-absorption, enhanced liver metabolism
Cellular Resistance |
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Term
| What 3 categories do Anticancer drugs fall into? |
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Definition
Action on DNA
Action of Mitotic Spindle
Hormonal Agents |
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Term
| What is Difinitive therapy? When is it effective? |
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Definition
Radiation or Surgery
Effective when metastasis has not occurred |
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Term
| What is used for treatment of breast and prostate tumors? |
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Definition
| Hormonal agonists/antagonists |
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Term
| What drugs are used for Renal Protection during chemotherapy? |
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Definition
Allopurinol Rasburicase
(protection from tumor lysis syndrome) |
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Term
| How does Allopurinol work? |
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Definition
Inhibits Xanthine oxidase->
Inhibits conversion of:
Hypoxanthine-> Xanthine
Xanthine-> Uric Acid |
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Term
| How does Rasburicase work? |
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Definition
Increases conversion of:
Uric acid-> Allantoin by Urate oxidase |
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Term
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Definition
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Term
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Definition
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Term
| What cancers are BCNU used to treat? |
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Definition
Brain cancers (crosses the BBB)
Astrocytoma Brain metastases Hodgkin's Non-Hodgkin's malignant glioma medulloblastoma multiple myeloma |
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Term
| How does Cyclophosphamide work? |
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Definition
| Transfer alkyl group to DNA Results in miscoding; strand breakage through guanine excision |
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Term
| Which alkylating agent especially causes problems in lungs? How? |
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Definition
Cyclophosphamide
Fibrosis |
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Term
| What metabolite of Cyclophophamide is Toxic to the Bladder? |
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Definition
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Term
| What alkylating drugs can produce Renal failure? How? |
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Definition
Cyclophosphamide
Proximal>>Distal tubules affected Difficulties in Ca and Mg reabsorption, glycosuria, renal tubular acidosis |
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Term
| How is Urotoxicity from acrolein prevented? |
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Definition
| Good Hydration co-administration of MESNA |
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Term
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Definition
Prophylactic chemoprotectant from hemorrhagic cystitis
(from Cyclophosphamide and Ifosfamide)
-Does not interfere with antitumor activity |
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Term
| Besides being used as a chemotherapy agent, what is cyclophosphamide used for? |
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Definition
| Preperation for allogenic stem cell transplantation Rheumatoid Arthritis |
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Term
| How is Busulfan metabolized? What are its toxicities? |
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Definition
Hepatic Metabolism Toxicity: Pulmonary Fibrosis Myelosuppression GI mucosal damage Veno-occlusive disease of liver
Addison's-like Syndrome
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Term
| What are side effects of Busulfan? |
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Definition
| Impotence, sterility, amenorrhea, fetal malformation |
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Term
| What Alkylating agent can cause asthenia and hypotension resembling Addison's disease, but with normal corticosteroids? |
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Definition
Busulfan
(also causes pulmonary fibrosis and veno-occlusive disease of liver)
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Term
| What Nitrosoureas carbamolyates proteins? |
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Definition
Carmustine (BCNU) via its metabolites
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Term
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Definition
| Alkylates and carbamolyates proteins |
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Term
| What allows BCNU to enter the CNS? |
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Definition
| Highly lipophilic and non-ionized at physiologic pH |
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Term
| What are the Toxicities of Carmustine (BCNU)? |
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Definition
CNS
Endocrine dysfunction with brain irradiation Encephalopathy, seizure, dementia
Veno-occlusive Disease of Liver
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Term
| What 2 drugs are associated with Hepatic veno-occlusive disease? |
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Definition
| Busulfan and BCNU (thiotepa, oxaliplatin, cytarabine, gemcitabine, thioguanine, actinomycin-D) |
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Term
| How does resistance occur to Carmustane (BCNU) ? |
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Definition
| Removal of the chloroethyl alkylation via AGT - same as Decarbazine |
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Term
| What drug is a polyfunctional aziridine alkylator formed by hydrolysis? |
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Definition
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Term
| How is Thiotepa administered and metabolised? |
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Definition
| IV, IVe(intravesicular), or IC(intracavity) Hepatic metabolism and elimination |
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Term
| What is the dose limiting toxicity of Thiotepa? |
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Definition
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Term
| What drug is a streptomyces-derived bioreductive alkylating agent? |
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Definition
Mitomycin C
Activated under reducing conditions (hypoxia)
Produces free radicals
Slow recovery from myelosuppresion |
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Term
| What problems are associated with Mitomycin C administration? |
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Definition
Bone Marrow suppression
-slow recovery, 8-week interval between 2nd and 3rd dose |
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Term
| What drugs are not metabolically activated? |
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Definition
| Platinum Drugs - Cisplatin |
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Term
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Definition
| Cl displaced by water, reacts with DNA and proteins |
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Term
| How is Cisplatin administered? |
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Definition
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Term
| What are the dose limiting toxicities of Cisplatin? |
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Definition
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Term
| What drug is a cytoprotective agent against Nephrotoxicity caused by Cisplatin? |
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Definition
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Term
| What drug can cause stocking glove syndrome? |
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Definition
| Cisplatin (may worsen with discontinuation of drug) |
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Term
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Definition
| Metabolically activated DNA methylating agent Myelosuppression, leukopenia and thrombocytopenia Side Fx: N/V common, 1-3 hours after therapy |
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Term
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Definition
Highly reactive DNA methylator via CYP activation
Causes chromatic breaks and translocations |
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Term
| How does resistance develop for Dacarbazine? |
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Definition
| removal of methyl groups from the O6-guanine vases by AGT |
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Term
| What drug has Disulfiram-like actions? |
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Definition
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Term
| What is the Mechanism of Action of Alkylating agents? |
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Definition
| Change the structure of DNA attack N7 of guanine of one strand then binds a second-> crosslinking of DNA |
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Term
| What is the mechanism of action of the Nitrogen Mustard (Cyclophosphamide)? |
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Definition
| Transfer an alkyl group to DNA at N7 guaine mainly (also N1, N3 adenine, N3 cytosine, O6 gyanine) |
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Term
| What does the crosslinking of DNA from Cyclophosphamide cause? |
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Definition
| miscoding, strand breakage through guanine excision |
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Term
| What cells are most susceptible to Nitrogen mustards? What does this cause? |
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Definition
| Replicating cells (G1-S) Causes G2 to be blocked |
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Term
| What drugs can cause Hepatic veno-occlusive disease? |
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Definition
Busulfan
Carmustine (BCNU) |
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Term
| When is mitomycin C most active? |
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Definition
Activated under reducing conditions
ie hypoxia-> more active at hypoxic tumor core |
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Term
| What are the dose limiting toxicities of Mitomycin C? |
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Definition
| Myelosuppression Injection site rxns |
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Term
| What Disease is Cisplatin associated with 4 years after treatment? |
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Definition
AML
(Acute Myeloid Lymphoma) |
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Term
| What can worsen the peripheral, motor and sensory neuropathy caused by Cisplatin? |
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Definition
| subsequent or simultaneous treatment with taxanes or other neurotoxic drugs |
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Term
| What is the Mechanism of AGT resistance? |
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Definition
| acceptor protein for O6-alkylguanine DNA monoadducts-> transfers alkyl group from DNA to the active site of the protein |
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Term
| Why is BCNU not used for Leukemia's? |
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Definition
|
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Term
| How can AGT inhibitors be used to treat cancers? |
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Definition
| may sensitize tumors to BCNU |
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Term
| What is the Mechanism of procarbazine? |
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Definition
| DNA methylator via Cyp activation-> damage(chromatid breaks, translocations) |
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Term
| Why does resistance to Procarbazine develop rapidly when used as a single agent? |
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Definition
| Guanine repair via guanine-O6 alkyl transferase Lacks cross resistance with other alkylators |
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