Dental Cancer2

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					Antineoplastic drugs/chemotherapy II Dental Pharmacology (PHCL 5-103) April 10, 2008

Hiroshi Hiasa, Ph.D. Office: 3-117 NHH Tel. 626-3101

Commonly Used Anticancer Drugs A. General Adverse Drug Effects (1) Most serious adverse effects are due to lack of selectivity between normal and cancer cells. (2) Side effects most noticeable in faster growing tissue hair, GI tract, bone marrow (3) Principal systematic adverse effects a. Bone marrow suppression leukopenia, anemia, thrombocytopenia b. Immune deficiency enhanced susceptibility to infection c. Susceptibility to additional cancers

B. DNA Binding and Modifying Drugs
A wide range of drugs that modify DNA/RNA through the addition of an alkyl group (cross-linking of the DNA).

(1) Alkylating agents a. Inhibit DNA replication and/or transcription Cell cycle-dependent b. Include: nitrogen mustards and nitrosoureas c. Effective in treatment of Leukemias, lymphomas, myelomas and carcinomas of the breast and ovary (2) Platinum coordination complexes (cisplatin) Used to treat metastatic testicular tumors and ovarian cancers


C. Cytotoxic antibiotics Cytotoxic antibiotics are used in treating a broad range of cancers (1) Bleomycin Binds to DNA and directly generates DNA breaks (DNA damage) (2) Actinomycin D (Dactinomycin) Intercalates between the bases in DNA and causes the inhibition of transcription (3) Anthracyclines - see topoisomerase inhibitors

D. Topoisomerase inhibitors (human topoisomerases I & II)
(1) Target topoisomerase II a. Etoposide (VP16) - non-intercalater b. Anthracyclines - intercalater Doxorubicin (Adriamycin) Daunorubicin (Daunomycin) (2) Target topoisomerase I Topotecan (3) Bind to a topoisomerase on DNA Cause inhibition of DNA replication and generation of DNA breaks. (4) Some of the most important drugs in treating a broad range of cancers

E. Antimetabolites Drugs that interfere with (indirectly inhibit) the synthesis of DNA and/or RNA (1) Folic acid analogues a. Folic acid is a cofactor that is required for the synthesis of thymidine and purines. b. Several drugs that are antagonists of folic acid are powerful antineoplastic agents. c. Methotrexate Used for the maintenance of remissions during the treatment of leukemia.


(2) Pyrimidine and purine analogues a. These are a class of compounds that are similar to the purines and pyrimidines. b. Inhibit some of the enzymes involved in DNA and RNA synthesis. c. 6-mercaptopurine A purine analogue that is used to treat some leukemias. d. Cytosine arabinoside An analogue of 2-deoxycytidine that is used to treat leukemias and some lymphomas.

F. Enzymes (1) Asparaginase a. Catalyzes the hydrolysis of asparagine to aspartic acid and ammonia. b. The effect is to inhibit protein synthesis by reducing the levels of available asparagine in malignant cells. c. Used to treat acute lymphocytic leukemia

G. Inhibition of mitosis Drugs that inhibit mitosis (1) Plant Alkaloids - vinblastine and vincristine a. Bind to the tubulin of the mitotic spindle, which blocks mitosis at metaphase. b. Effective against testicular tumors and Hodgkin’s Disease. c. Vincristine can produce neurotoxicity. (2) Taxol a. Inhibits mitosis by over-promoting the assembly of microtubules. b. Used in the treatment of ovarian and breast cancer.


H. Hormone Agonists and Antagonists (1) Neoplasms derived from prostate or mammory gland tissue are often dependent on hormones for their growth. a. Androgen and estrogen receptor antagonist (tamoxifen) used to treat breast cancer b. Estrogens (diethylstilbestrol, ethinyl estradiol) used to treat prostate cancer (2) Glucocorticoids Because of their ability to suppress mitosis in lymphocytes, have value in the treatment of some leukemias.

I. Biological response modifiers Stimulate a patient’s own biological response (1) Interleukin 2 Induces a T-cell response (2) All-trans-retinoic acid a. Can cause some neoplastic cells to exit the cell cycle by differentiating them into non-dividing cells. b. Has been used successfully to promote remission in some leukemias.

J. Personalized medicine (1) Diagnosis and treatment based on each patient's genotype, level of gene expression, especially oncogenes and tumor suppressor genes, other clinical information. (2) Provide the appropriate drug at the appropriate dose to each patient.


K. Dental Implications (1) Elective dental treatment is generally not performed during chemotherapy. Consult with the patient’s physician. (2) Infections are potentially lethal due to the immunosuppressed status of the patient. Any infection can delay the chemotherapy and reduce the chance of successful treatment.


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