Term
The antimetabolites used to treat cancer have structures that are very similar to those of compounds involved in the biosynthesis of ______.
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Definition
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Term
| Name the 3 categories of antimetabolites... |
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Definition
antifolates, antipyrimidines, and antipurines
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Term
| Folic acid (pteroylglutamic acid), a member of the B-vitamin complex, is widely distributed in plants and is comprised of three components: |
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Definition
| a pteridine ring system, para-aminobenzoic acid (PABA), and glutamic acid |
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Term
| The addition of glutamate residues (by either polyglutamation or polyglutamylation) increases what 2 things? |
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Definition
1) molecular weight
2) overall negative charge of the molecule (which decreases efflux from the cell) |
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Term
Folic acid is activated in the cell by conversion to its dihydro- and tetrahydro- forms by sequential reduction by which enzyme?
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Definition
| Dihydrofolate reductase (DHFR) |
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Term
| What antimetabolite drug class does methotrexate belong to? |
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Definition
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Term
| What was the first anti-folate drug to demonstrate effectiveness in acute leukemias in 1948? |
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Definition
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Term
| Methotrexate is a potent DHFR inhibitor. It produces an acute _______ _______ of folate coenzymes. |
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Definition
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Term
| MTX's antiproliferative effects have been used in treating what other conditions (not cancer)? |
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Definition
| Psoriasis and a number of inflammatory conditions (including RA) |
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Term
| Name some cancers in which MTX is useful... |
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Definition
Breat cancer
Acute lymphocytic leukemia in CHILDREN
Choriocarcinoma in WOMEN
Osteogenic sarcoma |
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Term
| MTX is considered a ____ ____ specific drug because it targets DNA/RNA synthesis during the __ phase of mitosis (the phase in which DNA synthesis is the highest). |
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Definition
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Term
| MTX also blocks the synthesis of the pyrimidine base thymidine by blocking which 2 enzymes? |
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Definition
DHFR
TS (thimidylate synthetase) |
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Term
| High-dose methotrexate often is used with _____, also known as _____, citrovorum factor, or folinic acid to treat osteogenic sarcoma and acute leukemias. |
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Definition
N-formyltetrahydrofolate
leucovorin |
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Term
| What is leucovorin rescue therapy? |
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Definition
| It involves the administration of potentially lethal doses of MTX to block reduced folate synthesis in both normal and neoplastic cells. Subsequent administration of leucovorin selectively rescues the normal cells from the toxic effects of MTX while leaving the cancer cells to die. Leucovorin's ability to selectively rescue normal cells as opposed to tumor cells probably resides in its poor transportability into malignant cells |
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Term
Tumor cells acquire resistance to MTX through a variety of different mechanisms...
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Definition
(1) Impaired transport of the drug into cells
(2) Production of altered forms of DHFR having decreased affinity for MTX.
(3) Increased concentrations of DHFR. Upon initial MTX exposures, DHFR appears to bind to its own mRNA and improve its translational efficiency. Longer exposures result in production of multiple copies of the DHFR gene (gene amplification).
(4) Decreased ability to synthesize MTX polyglutamates.
(5) Decreased thymidylate synthetase activity. |
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Term
| What drug is approved for the treatment of mesothelioma, a cancer caused by the exposure to asbestos? |
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Definition
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Term
| Major toxicity of pemetrexed is _______. Patients taking this drug should take ______ and ______ daily to reduce toxicity effects. |
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Definition
Myelosuppression
Folic acid and Vitamin B12
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Term
| What class of antimetabolites does pemetrexed belong to? |
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Definition
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Term
| What class of antimetabolites does pralatrexate (Folotyn) belong to? |
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Definition
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Term
| What type of cancer is pralatrexate used for? |
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Definition
| Peripheral T-cell lymphoma |
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Term
| Oldest drug of the pyrimidine antagonists drug class is... |
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Definition
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Term
| 5-FU is administered ________ mostly in combination chemotherapy for treatment of ______ and ______ cancers. |
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Definition
Parenterally
GI and breast |
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Term
| Floxuridine (FUDR) is used primarily by _____ _____ into the hepatic artery for treatment of metastatic carcinoma of the _____. |
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Definition
continuous infusion
colon |
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Term
| Capecitabine (Xeloda) is a prodrug of _____ and is used ______ for the treatment of _______ ______ cancer for patients who have not responded to other agents such as taxol or anthracyclines. |
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Definition
5-FU
orally
metastatic breast |
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Term
| What antimetabolite drug class does capecitabine belong to? |
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Definition
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Term
| Cytarabine (cytosine arabinoside, ARA-C) is used in which type of cancer treatment? |
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Definition
| acute myelocytic leukemia |
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Term
| Which antimetabolite drug class does cytarabine belong to? |
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Definition
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Term
| Catalyzed by deoxycytidine kinase, ARA-C is activated by the conversion first to the _____________. |
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Definition
| 5'-monophosphate nucleotide (ARA-CMP) |
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Term
| Gemcitabine (Gemzar) is administered by IV infusion and is used in treating which types of cancer? |
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Definition
Metastatic pancreatic cancer
Non-small cell lung cancer
Melanoma
Ovarian cancer |
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Term
| Gemcitabine is a member of which antimetabolite drug class? |
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Definition
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Term
| In the cell, gemcitabine is converted into its 5'-di- and tri-phosphates. The ___________ is a potent inhibitor of ribonucleotide reductase. |
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Definition
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Term
| This antimetabolite drug is considered the sulfur analog of hypoxanthine... |
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Definition
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Term
| 6-MP is used orally as maintenance therapy in the treatment of which cancer? |
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Definition
| acute lymphocytic leukemia |
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Term
| This antimetabolite drug is considered the sulfur analog of guanine... |
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Definition
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Term
| Thioguanine is used orally in the treatment of which cancer? |
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Definition
| Acute granulocytic leukemia |
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Term
| 6-MP and thioguanine belong to which antimetabolite drug class? |
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Definition
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Term
| Allopurinol (Zyloprim) blocks the conversion of 6-MP to 6-thiouric acid and the production of uric acid from hypoxanthine and xanthine. Allopurinol belongs to which drug class? |
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Definition
| xanthine oxidase inhibitor |
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Term
| Deficiency of this gene will cause severe toxicity with 6-MP administration. |
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Definition
| thiopurine methyltransferase (TPMT) |
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Term
| Pentostatin (Nipent) is a transition-state analog of the intermediate formed in the conversion of adenosine to inosine by which enzyme? |
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Definition
| Adenosine deaminase (ADA) |
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Term
| Pentostatin is used in the treatment of which type of cancer? |
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Definition
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Term
| Pentostatin belong to which group of antimetabolites? |
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Definition
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Term
| This is the preffered drug for treatment of hairy cell leukemia and it is also effective in treating MS. |
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Definition
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Term
| Fludarabine (Fludara) is a purine analog and is used in the treatment of which type of cancer? |
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Definition
| Chronic lymphocytic leukemia |
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Term
| Clofarabine (Clolar) is a purine antagonists approved for pediatric patients for relapsed or refractory __________, after at least 2 prior regimens. |
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Definition
| acute lymphoblastic leukemia |
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Term
| Nelarabine (Arranon) is a purine antagonist that is FDA approved for refractory or relapsed ____________ and __________ cancers that have not responded to 2 prior regimens. |
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Definition
T-cell acute lymphoblastic leukemia
T-cell lymphoblastic lymphoma |
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Term
| _________ _________ is a key cellular enzyme that converts ribonucleotides to 2'-deoxyribonucleotides, a reaction vital for DNA synthesis. |
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Definition
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Term
| Two well-established inhibitors of nucleotide reductase are... |
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Definition
| gemcitabine and hydroxyurea |
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Term
| Hydroxyurea can be used (orally) in a variety of conditions. |
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Definition
chronic myelocytic leukemia, sickle cell disease, essential thrombocytosis
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