Chemotherapy

Chemotherapy is the use of chemical substances to treat disease. In its modern-day use, it refers almost exclusively to cytostatic drugs used to treat cancer.

Types and dosage

The majority of chemotherapeutic drugs can be divided in to: alkylating agents, antimetabolites, plant alkaloids, topoisomerase inhibitors, and antitumour agents. All of these drugs affect cell division or DNA synthesis and function in some way.

Related Topics:
Alkylating agent - Antimetabolite - Alkaloid - Topoisomerase - Cell division - DNA

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Some newer agents don't directly interfere with DNA. These include the new tyrosine kinase inhibitor imatinib mesylate (Gleevec® or Glivec®), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors).

Related Topics:
Tyrosine kinase - Imatinib mesylate - Chronic myelogenous leukemia - Gastrointestinal stromal tumor

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In addition, some drugs may be used which modulate tumour cell behaviour without directly attacking those cells. Hormone treatments fall into this category of adjuvant therapies.

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Dosage of chemotherapy can be difficult: if the dose is too low, it will be ineffective against the tumor, while at excessive doses the toxicity (side-effects, neutropenia) will be intolerable to the patient. This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity. In immunotherapy, they are in principle used in smaller dosages than in the treatment of malign diseases.

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In most cases, the dose is adjusted for the patient's body surface area, a composite measure of weight and height that mathematically approximates the body volume. The BSA is usually calculated with a mathematical formula or a nomogram, rather than by direct measurement.

Related Topics:
Body surface area - Nomogram

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Alkylating agents

Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumour growth by cross-linking guanine nucleobases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs acts mainly nonspecifically, some of them requires conversion into active substances in vivo (e.g. cyclophosphamide).

Related Topics:
Alkylating agent - Electronegative - Guanine - Nucleobase - DNA - Cyclophosphamide

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Cyclophosphamide is one of the most potent immunosuppressive substances. In small dosages, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune hemolytic anemias, Wegener's granulomatosis and other autoimmune diseases. High dosages cause pancytopenia and hemorrhagic cystitis. Other selected examples: cisplatin, carboplatin, ifosfamide, chlorambucil, busulfan, thiotepa, nitrosoureas and others.

Related Topics:
Hemolytic anemias - Wegener's granulomatosis - Autoimmune disease - Pancytopenia - Cystitis - Cisplatin - Carboplatin - Ifosfamide - Chlorambucil - Busulfan - Thiotepa - Nitrosourea

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Anti-metabolites

Anti-metabolites masquerade as purine ((azathioprine, mercaptopurine)) or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used cytostatics. An important example is 5-fluorouracil (5FU), which inhibits thymidylate synthase. Fludarabine inhibits function of multiple DNA polymerases, DNA primase, DNA ligase I and is S phase-specific (since these enzymes are highly active during DNA replication).

Related Topics:
Anti-metabolite - Purine - Mercaptopurine - Pyrimidine - Cell cycle - 5-fluorouracil - Thymidylate synthase - Fludarabine

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Methotrexate, a folic acid analogue, prevents the formation of tetrahydrofolate, essential for purine and pyrimidine synthesis, by inhibiting dihydrofolate reductase. This leads to inhibited production of DNA, RNA and proteins (as tetrahydrofolate is also involved in the synthesis of amino acids serine and methionine).

Related Topics:
Methotrexate - Folic acid - Dihydrofolate reductase - Serine - Methionine

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Azathioprine is the main immunosuppressive cytotoxic substance. It is widely used in transplantations to control rejection reactions. It is nonenzymatically cleaved to 6-mercaptopurine that acts as a purine analogue and an inhibitor of DNA synthesis. By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity. It also successfully suppresses autoimmunity.

Related Topics:
Azathioprine - Cell - Humoral immunity

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Plant alkaloids

These alkaloids are derived from plants and block cell division by preventing microtubule function. Microtubules are vital for cell division and without them it can not occur. The main examples are vinca alkaloids and taxanes.

Related Topics:
Alkaloid - Plant - Microtubule - Vinca alkaloid - Taxane

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Vinca alkaloids

Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules (M phase of the cell cycle). They are derived from the Madagascar periwinkle, Catharanthus roseus (formerly known as Vinca rosea). The vinca alkaloids include: -

Related Topics:
M phase - Cell cycle - Madagascar periwinkle

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• Vincristine
• Vinblastine
• Vinorelbine
• Vindesine

Podophyllotoxin

Podophyllotoxin is a plant-derived compound used to produce two other cytostatic drugs, etoposide and teniposide. They prevent the cell from entering the G1 phase (the start of DNA replication) and the replication of DNA (the S phase). The exact mechanism of its action still has to be elucidated.

Related Topics:
Podophyllotoxin - Etoposide - Teniposide - G1 phase - S phase

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The substance has been primarily obtained from the American mayapple (Podophyllum peltatum). Recently it has been discovered that a rare Himalayan Mayapple (Podophyllum hexandrum) contains it in a much greater quantity, but as the plant is endangered, its supply is limited. Studies have been conducted to isolate the genes involved in the substance's production, so that it could be obtained recombinantively.

Related Topics:
American mayapple - Himalayan Mayapple - Recombinantively

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Taxanes

Taxanes are derived from the Pacific yew tree, Taxus brevifolia. Taxanes enhance stability of microtubules, preventing the separation of chromosomes during anaphase. Taxanes include: -

Related Topics:
Pacific yew tree - Chromosome - Anaphase

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• Paclitaxel
• Docetaxel

Topoisomerase inhibitors

Topoisomerases are essential enzymes that maintain the topology of DNA. Inhibition of type I or type II topoisomerases interferes with both transcription and replication of DNA by upsetting proper DNA supercoiling. Some type I topoisomerase inhibitors include camptothecins: irinotecan and topotecan. Examples of type II inhibitors include amsacrine, etoposide, etoposide phosphate, and teniposide. The latter are semisynthetic derivatives of epipodophyllotoxins, alkaloids naturally occurring in the root of mayapple (Podophyllum peltatum) .

Related Topics:
Topoisomerase - Enzyme - Topology - Transcription - Replication - Supercoil - Irinotecan - Topotecan - Amsacrine - Etoposide - Etoposide phosphate - Teniposide - Epipodophyllotoxin

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Antitumour antibiotics

There are many differing antitumour antibiotics, but generally they prevent cell division by several ways: (1) binding to DNA through intercalation between two adjacent nucleotide bases and making it unable to separate, (2) inhibiting ribonucleic acid (RNA), preventing enzyme synthesis, (3) interfering with cell replication. They are products of various strains of the soil fungus Streptomyces. Examples are anthracyclines (doxorubicin, daunorubicin and epirubicin, which also inhibit topoisomerase II), actinomycin, bleomycin, mitomycin and plicamycin. Bleomycin acts in unique way through oxidation of a DNA-bleomycin-Fe(II) complex and forming free radicals, which induce damage and chromosomal aberrations. The most important immunosuppressant from this group is dactinomycin, which is used to in kidney transplantations.

Related Topics:
Antitumour antibiotic - Intercalation - Anthracycline - Doxorubicin - Daunorubicin - Epirubicin - Bleomycin - Mitomycin - Dactinomycin - Kidney transplantation

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Hormonal therapy

Several malignancies responds to hormonal therapy. Strictly speaking, this is not chemotherapy. Cancer arising from certain tissues, including the mammary and prostate glands, may be inhibited or stimulated by appropriate changes in hormone balance.

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• Steroids (often dexamethasone) can inhibit tumour growth or the associated edema (tissue swelling), and may cause regression of lymph node malignancies.
• Prostate cancer is often sensitive to finasteride, an agent that blocks the peripheral conversion of testosterone to 5-hydroxy-testosterone.
• Breast cancer cells often highly express the estrogen and/or progesterone receptor. Inhibiting the production (with aromatase inhibitors) or action (with tamoxifen) of these hormones can often be used as an adjunct to therapy.
• Gonadotropin-releasing hormone agonists (GnRH), such as goserelin possess a paradoxic negative feedback effect followed by inhibition of the release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone), when given continuously.

Some other tumours are also hormone dependent, although the specific mechanism is still unclear.

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