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Cancer Chemotherapy
Cancer themotherapy drugs
67
Pharmacology
Undergraduate 2
03/17/2011

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Term
cancer cells that leave primary tumor, travel through lymphatic and blood vessels and colonize distance sites; poor prognosis
Definition
metastases
Term
imbalance in cell proliferation and cell death (apoptosis)
Definition
Cancer
Term
- failure of early detection
-100% kill required
-drug resistance
Definition
challenges of chemo
Term
cancer cells lack________
Definition
contact inhibition
Term
when normal cells touch each other they normally stop growing and this maintains tissue architecture. This is called _________
Definition
contact inhibition
Term
these are used when a tumor is accessible
Definition
1. radiation
2. surgery
Term
these cancer treatments are used when the tissue is not accessible
Definition
1. chemotherapy
2. hormonal therapy
3. antibodies and immunotherapy
4. combinations
Term
this cancer drug resistance is the loss/mutation of tumor supressors
Definition
intrinsic
Term
this cancer drug resistance is when the tumor responds to single drug initially but over time develops resistance
Definition
acquired
Term
the loss of this enzyme in about half of all tumors causes therapeutic resistance
Definition
p53
Term
acquired resistance is usually due to the loss of a cell surface pump called ______
Definition
MDR-1
Term
bone marrow suppression, increased risk of infection, mucositis, nausea, vomiting, wasing, alopecia, reproductive system damage, neurotoxcitity, dna damage
Definition
side effects of chemotherapy
Term
how do you minimize side effects for chemo?
Definition
optimize the way and amount of drug given on an intermittent basis
Term
why is combination therapy important?
Definition
reduces the likelihood of resistance
Term
why is combination therapy important?
Definition
reduces the likelihood of resistance
Term
drugs that really target the causative molecular abnormalities at work
Definition
rationally-designed drugs
Term
these don't target the tumor at all, but enable the patient to tolerate toxic chemotherapy better
Definition
supportive therapy
Term
what do cancer drugs inhibit?
Definition
DNA synthesis, division, RNA divison
Term
chemotherapeutic drugs active only in specific cell cycle phases
Definition
cell cycle specific (CCS)
Term
CCS drugs that inhibit DNA synthesis
Definition
antimetabolites, topoisomerase inhibitors
Term
CCS drugs that inhibit chromosome segregation in the M phase
Definition
microtubule inhibitors
Term
chemotherapeutic drugs that target both resting and dividing cells
Definition
cell cycle nonspecific (CCNS)
Term
CCNS drugs that inhibit gene expression
Definition
alkylating agents, antibiotics, estrogen/androgen antagonists
Term
structural analogs of molecules required for the syntheis of DNA and only function in tumor cells in the S PHASE
Definition
antimetabolites
Term
these drugs are most effective for rapidly proliferating tumors like leukemias and lymphoma but they also target healthy cells
Definition
antimetabolits
Term
most widely used antimetabolit in cancer chemo. most effective fro pediatric ALL, choriocarcinoma
Definition
methotrexate
Term
what does methotrexate inhibit?
Definition
dihydrofolate reductase
Term
main side effects of methotrexate
Definition
bone marrow supression, nephrotoxicity
Term
vincristine
vinblastine
Definition
vinca alkaloids (microtubule inhibitors)
Term
microtubules are required for the normal function of
Definition
neurons
Term
paclitaxel
docetaxel
Definition
taxanes (microtubule inhibitors)
Term
main side effect of microtubule inhibitors
Definition
neurotoxicity
Term
why do tumor cells become resistant to microtubule inhibitors?
Definition
mdr-1 gene
Term
this is required for DNA synthesis
Definition
topoisomerase inhibitors
Term
this topoisomerase inhibitor is used to treat testicular cancer, small lung carcinoma but has resistance to the MDR1 gene
Definition
etoposide
Term
The pumping by the MDR-1 pump results in
Definition
less drug in the cell available for effective treatment
Term
is MDR selective for any particular drug?
Definition
NO
Term
- intercalate into DNA and prevent transcription
-cause single strand DNA breaks
_generally cell cycle non-specific
Definition
antibiotice- dna intercalating drugs
Term
widely used antibiotic
minimally myelo- and immunosuppressive
Definition
bleomycin
Term
side effects of bleomycin
Definition
pulmonary fibrosis
rare liver failure in lymphoma pts
Term
highly reactive compounds that modify DNA and cellular proteins can cause secondary cancer and induce leukemia
Definition
Alkylating Agents
Term
Nitrogen Mustards
platnium compounds
nitrosoureas
alkyl sulfonates
Definition
alkylating agents
Term
This nitrogen mustard is very broad spectrum side effects are potent immunosuppression GI ulcers, alopecia, and nausea
Definition
cyclophosphamide
Term
These platnium compounds are very effective when combined with other drugs but may cause nephrotoxcitiy, hearing problems, and peripheral neuropathy
Definition
cisplatin, carboplatin
Term
tumor cells that are mutant against p53 have an intrinsic resistance of which class of drugs?
Definition
alkylating agents
Term
this rationally designed chemotherapeutic is an inhibitor of the bcr-abl tyrosine kinase causative for chronic myelocytic leukemia- remarkable singla agent therapy with few side effects
Definition
Imatinib (Gleevec)
Term
mutations in the bcr-abl that cause resistance can be identified and modified to fit the patient
Definition
pharmacogenics of imatinib
Term
breast and prostate tumors frequently require _______&_______ for growth
Definition
estrogen/androgen
Term
side effects of _________ are relatively minor
Definition
hormonal agents
Term
first choice for hormonal therapy of estrogen receptor + breast cancer
Definition
anti-estrogens
Term
tamoxifen
raloxifene
Definition
anti estrogens that are safe and approved for treatment and prevention of breast cancer
Term
ihibit binding of circulating estradiol to the ER and subsequent gene transcription
Definition
anti-estrogen mechanism of action
Term
anti-estrogens are useless in_______
Definition
premenopausal women and ER - tumors
Term
useful in the treatment of prostate cancer
Definition
anti-androgens
Term
steroidal anti-androgen inhibit binding to the AR
Definition
cyproterone
Term
non-steroidal anti-androgens inhibit nuclear translocation of the AR
Definition
bicalutamide
Term
inhibit AR-dependant gene transcription
Definition
anti-androgen MOA
Term
vaccine angainst HPV 6,11,16, and 18 . # 16 and 18 cause cervical cancer. Effective only as a prophylactic
Definition
Gardasil
Term
why is gardasil not a substitute for the current standard of care?
Definition
routine screening and intervention detect 75% of cervical cancers. and there are other causes of cancer
Term
what is the major side effect of antibodies?
Definition
hypersensitivity
Term
this humanized antibody binds CD20 found on 90% of non-hodgkins lymphomas and can be conjugated with radioactive iodine
Definition
Rituximab
Term
antibody to human epidermal growth factor recepto 2 to treat metastatic breast cancers
Definition
Trastuzumab
Term
kill cells in multiple phases of the cell cycle, and lowers the risk of acquired resistance
Definition
combination therapies
Term
granulocyte colony stimulating factor, prophulaxis of chemotherapy-induced neutropenia
Definition
Filgrastim (Neupogen)
Term
folate supplement to modulate cytotoxicity
Definition
Leucovorin
Term
granulocyte/ macrophage colony-stimulating factor aids neutrophil recovery in AML pts
Definition
Sargramostim
Term
prevents hypercalcemia and bone asociated with malignancy
Definition
pamidronate
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