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Anti-Cancer Agents
n/a
62
Other
Post-Graduate
11/21/2011

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Cards

Term
Proto-oncogenes
Definition
Unaltered, normal allele of gene that controls cellular growth and differentiation
Term
Oncogene
Definition
Potentially cancer causeing gene
Proto-oncogene that has been altered by a carcinogenic agent
Term
Tumor supressor genes
Definition
Encode proteins that inhibit cell division and trigger apoptosis
Term
What are the 6 hallmarks of Cancer Cells?
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
Term
What is the Gompertzian theory of cell growth?
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
Term
What assumptions are the Goldie-Coldman Hypthesis based on?
Definition
-Tumors have an inherently higher rate vs. normal cells
-With progression, there appears to be a continued increase in mutation rate
Term
What are the Goldie-Coldman Hypothesis?
Definition
Mutations randomly result in altered phenotypes that confer cellular resistance to chemotherapeutic drugs
-Probability of resistance cells depends on tumor size.
Term
What types of Mechanisms cause chemotherapeutic failure?
Definition
Kinetic Resistance
-Slow-growing, poor vascularization
Pharmacological Resistance
-Pharmacological sanctuary, non-absorption, enhanced liver metabolism
Cellular Resistance
Term
What 3 categories do Anticancer drugs fall into?
Definition

Action on DNA

Action of Mitotic Spindle

Hormonal Agents

Term
What is Difinitive therapy? When is it effective?
Definition
Radiation or Surgery
Effective when metastasis has not occurred
Term
What is used for treatment of breast and prostate tumors?
Definition
Hormonal agonists/antagonists
Term
What drugs are used for Renal Protection during chemotherapy?
Definition

Allopurinol Rasburicase

(protection from tumor lysis syndrome)

Term
How does Allopurinol work?
Definition
Inhibits Xanthine oxidase->
Inhibits conversion of:
Hypoxanthine-> Xanthine
Xanthine-> Uric Acid
Term
How does Rasburicase work?
Definition
Increases conversion of:
Uric acid-> Allantoin by Urate oxidase
Term
Nitrogen mustard drug
Definition
Cyclophosphamide
Term
Platinum drug
Definition
Cisplatin
Term
What cancers are BCNU used to treat?
Definition

Brain cancers (crosses the BBB)

Astrocytoma Brain metastases Hodgkin's Non-Hodgkin's malignant glioma medulloblastoma multiple myeloma

Term
How does Cyclophosphamide work?
Definition
Transfer alkyl group to DNA Results in miscoding; strand breakage through guanine excision
Term
Which alkylating agent especially causes problems in lungs? How?
Definition

Cyclophosphamide

Fibrosis

Term
What metabolite of Cyclophophamide is Toxic to the Bladder?
Definition

Acrolein

 

Term
What alkylating drugs can produce Renal failure? How?
Definition

Cyclophosphamide

Proximal>>Distal tubules affected Difficulties in Ca and Mg reabsorption, glycosuria, renal tubular acidosis

Term
How is Urotoxicity from acrolein prevented?
Definition
Good Hydration co-administration of MESNA
Term
What is MESNA used for?
Definition

Prophylactic chemoprotectant from hemorrhagic cystitis

(from Cyclophosphamide and Ifosfamide)

-Does not interfere with antitumor activity

Term
Besides being used as a chemotherapy agent, what is cyclophosphamide used for?
Definition
Preperation for allogenic stem cell transplantation Rheumatoid Arthritis
Term
How is Busulfan metabolized? What are its toxicities?
Definition

Hepatic Metabolism Toxicity: Pulmonary Fibrosis Myelosuppression GI mucosal damage Veno-occlusive disease of liver

Addison's-like Syndrome

Term
What are side effects of Busulfan?
Definition
Impotence, sterility, amenorrhea, fetal malformation
Term
What Alkylating agent can cause asthenia and hypotension resembling Addison's disease, but with normal corticosteroids?
Definition

Busulfan

(also causes pulmonary fibrosis and veno-occlusive disease of liver)

Term
What Nitrosoureas carbamolyates proteins?
Definition

Carmustine (BCNU) via its metabolites

 

Term
How does BCNU work?
Definition
Alkylates and carbamolyates proteins
Term
What allows BCNU to enter the CNS?
Definition
Highly lipophilic and non-ionized at physiologic pH
Term
What are the Toxicities of Carmustine (BCNU)?
Definition

CNS

Endocrine dysfunction with brain irradiation Encephalopathy, seizure, dementia

 

Veno-occlusive Disease of Liver

 

Term
What 2 drugs are associated with Hepatic veno-occlusive disease?
Definition
Busulfan and BCNU (thiotepa, oxaliplatin, cytarabine, gemcitabine, thioguanine, actinomycin-D)
Term
How does resistance occur to Carmustane (BCNU) ?
Definition
Removal of the chloroethyl alkylation via  AGT - same as Decarbazine
Term
What drug is a polyfunctional aziridine alkylator formed by hydrolysis?
Definition
Thiotepa
Term
How is Thiotepa administered and metabolised?
Definition
IV, IVe(intravesicular), or IC(intracavity) Hepatic metabolism and elimination
Term
What is the dose limiting toxicity of Thiotepa?
Definition
Neurotoxicity
Term
What drug is a streptomyces-derived bioreductive alkylating agent?
Definition

Mitomycin C

Activated under reducing conditions (hypoxia)

Produces free radicals

Slow recovery from myelosuppresion

Term
What problems are associated with Mitomycin C administration?
Definition
Bone Marrow suppression
-slow recovery, 8-week interval between 2nd and 3rd dose
Term
What drugs are not metabolically activated?
Definition
Platinum Drugs - Cisplatin
Term
How does cisplatin work?
Definition
Cl displaced by water, reacts with DNA and proteins
Term
How is Cisplatin administered?
Definition
IV only
Term
What are the dose limiting toxicities of Cisplatin?
Definition
Nephrotoxic
Ototoxicity
Term
What drug is a cytoprotective agent against Nephrotoxicity caused by Cisplatin?
Definition
Amifostine
Term
What drug can cause stocking glove syndrome?
Definition
Cisplatin (may worsen with discontinuation of drug)
Term
What is Dacarbazine?
Definition
Metabolically activated DNA methylating agent Myelosuppression, leukopenia and thrombocytopenia Side Fx: N/V common, 1-3 hours after therapy
Term
What is Procarbazine?
Definition
Highly reactive DNA methylator via CYP activation
Causes chromatic breaks and translocations
Term
How does resistance develop for Dacarbazine?
Definition
removal of methyl groups from the O6-guanine vases by AGT
Term
What drug has Disulfiram-like actions?
Definition
Procarbazine
Term
What is the Mechanism of Action of Alkylating agents?
Definition
Change the structure of DNA attack N7 of guanine of one strand then binds a second-> crosslinking of DNA
Term
What is the mechanism of action of the Nitrogen Mustard (Cyclophosphamide)?
Definition
Transfer an alkyl group to DNA at N7 guaine mainly (also N1, N3 adenine, N3 cytosine, O6 gyanine)
Term
What does the crosslinking of DNA from Cyclophosphamide cause?
Definition
miscoding, strand breakage through guanine excision
Term
What cells are most susceptible to Nitrogen mustards? What does this cause?
Definition
Replicating cells (G1-S) Causes G2 to be blocked
Term
What drugs can cause Hepatic veno-occlusive disease?
Definition

Busulfan

Carmustine (BCNU)

Term
When is mitomycin C most active?
Definition
Activated under reducing conditions
ie hypoxia-> more active at hypoxic tumor core
Term
What are the dose limiting toxicities of Mitomycin C?
Definition
Myelosuppression Injection site rxns
Term
What Disease is Cisplatin associated with 4 years after treatment?
Definition

AML

(Acute Myeloid Lymphoma)

Term
What can worsen the peripheral, motor and sensory neuropathy caused by Cisplatin?
Definition
subsequent or simultaneous treatment with taxanes or other neurotoxic drugs
Term
What is the Mechanism of AGT resistance?
Definition
acceptor protein for O6-alkylguanine DNA monoadducts-> transfers alkyl group from DNA to the active site of the protein
Term
Why is BCNU not used for Leukemia's?
Definition
High AGT in leukemia
Term
How can AGT inhibitors be used to treat cancers?
Definition
may sensitize tumors to BCNU
Term
What is the Mechanism of procarbazine?
Definition
DNA methylator via Cyp activation-> damage(chromatid breaks, translocations)
Term
Why does resistance to Procarbazine develop rapidly when used as a single agent?
Definition
Guanine repair via guanine-O6 alkyl transferase Lacks cross resistance with other alkylators
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