W
hat is Biology Good For?
Killing Cancer Cells: Chemotherapy Drugs

(This assignment is optional. Read this essay and answer the questions at the bottom for 3 extra credit points. You may only turn in one per six weeks. The assignment is due one week before the end of the six weeks. It is not necessary to visit the links in the text unless you are interested in more information.)

 


Common Chemotherapy Drugs

You probably know someone, maybe a friend or family member, who has been diagnosed with cancer. If the cancer is found to be benign, usually the recommended course of treatment is removel of the tumor, followed by radiation therapy to destroy any remaining cancer cells at the site of the orginal tumor. If pathologists determine that the cancer cells are malignant (have travelled to the lymph nodes, or have cellular characteristics that suggest malignancy), a recommended course of treatment chemotherapy, sometimes called "chemo" - a slang term meaning "drug therapy with chemicals".

Most chemo drugs are known as "anti-neoplastics". [anti-nee-oh-PLAS-tics.], neoplastics being cancer cells. Most antineoplastics work by stopping cell division in one or another stage of the cell cycle. They cause cell death in any dividing cell, and since most human cells are not dividing all the time, they preferentially kill cancer cells. But any human cell types which divide frequently are also killed: cells in the gastrointestional tract, the bone marrow, and hair follicles. These are reversible processes and will symptoms will disappear when the drug is discontinued. (But the cancer cells will be hopefully killed by then). [Quote]

The most common drugs used for newly diagnosed cancer are Cyclophosphamide (Cytoxan), Methotrexate, 5-Fluorouracil (5-FU) and Doxorubicin (Adriamycin). These are often given in combination: CMF - which stands for Cytoxan, Methotrexate and 5-Fluorouracil, AC - for Adriamycin and Cytoxan, or CAF (or FAC) - Cytoxan, Adriamycin, and 5-Fluorouracil.


Adriamycin
Generic Name: Doxorubicin

Mode of Action: 
Adriamycin prevents
DNA replication. The exact mechanism is still being studied, but it may be a "topoisomerase inhibitor". Topoisomerases are enzymes that temporarily cut one strand of DNA during replication to help unwind the double helix.. Adriamycin prevents the topoisomerase from reattaching the cut ends. A new version of doxorubicin 'wrapped up' in a lipid coat (liposome) called Doxil has been recently approved as a Kaposi's sarcoma treatment.

Common Side Effects: hair loss, mouth sores, nausea, vomiting, lowered blood counts (WBCs, RBCs and platelets), damage to the heart muscle, skin damage if drug leaks out of vein during infusion.


Cytoxan
Generic Name: Cyclophosphamide

Mode of Action: Interferes with
DNA synthesis and replication. Cytoxan is a drug that cross-links with the nucleotides of DNA. When cross-linked with Cytoxan, the DNA double helix is unable to unwind, DNA replication does not occur, and the cells die.

Common side effects: Cytoxan is one of the nastier chemo drugs, with lots of side effects. Side effects include lowered blood counts (WBCs, Platelets, RBCs), nausea, vomiting, loss of appetite, hair loss, loss of menstrual periods, decreased sex drive, bladder irritation, metallic taste in mouth during injection.


5FU or Adrucil
Generic Name: 5-Fluorouracil

Mode of Action:  Stops DNA synthesis and replication by inhibiting the enzyme thymidylate synthetase, involved in the incorporation of the nucleotide T into the DNA during replication.

Common Side Effects: mild nausea, vomiting, loss of appetite, thinning or loss of hair, skin rash and itching, skin darkening, weakness.



Mexate, Emtexate, Metatrexan, Methopterin, or Folex
Generic Name:
Methotrexate

Mode of Action: Blocks actively dividing cells from making nucleotides. Methotrexate competes in the cell for an enzyme called folic acid reductase, and prevents the synthesis of tetrahydrofolate, a chemical used by the cell for making nucleotides. Without nucleotides, DNA synthesis cannot proceed.

Common side effects: mouth sores, nausea, vomiting, loss of appetite, upset stomach, skin and eye sensitivity to sunlight, abnormal liver function tests, hair loss, anemia.


Taxol
Generic Name: Paclitaxel

Mode of Action:  Taxol (Paclitaxel) was first isolated from the from the bark of the Pacific Yew tree (Taxus brevifolia). Taxol disrupts the balance between tubulin and microtubule fibers, causing the formation of abnormal microtubule bundles. This prevents dividing cells from moving chromosomes to their "daughter" cells by interfering with spindle fiber formation.

Common side effects: Allergic reaction such as low blood pressure, shortness of breath, rash; loss of hair; low blood cell counts; nerve pain.


Oncovin, Vincasar, Vincrex, or Leurocristine
Generic Name:
Vincristine

Mode of Action:
Prevents the formation of spindle fibers during metaphase of mitosis. Vincristine is an alkaloid isolated from the Madagascar periwinkle, Catharantus roseus, formerly classified as Vinca rosea, which led to it being called a Vinca alkaloid, and thus vincristine. It binds to tubulin, the protein that makes up the spindle fiber microtubules, and prevents metaphase of mitosis.

Common side effects: bloating, nausea and vomiting, skin rash, temporary loss of hair, neurological problems



Leukerin, Mercaleukin, or Puri-Nethol
Generic Name:
6-Mercaptopurine, or 6-MP

Mode of Action: Inhibits the synthesis of the purine nucleotides A and G necessary for DNA synthesis; may also mimic A and G during DNA replication and stop further DNA synthesis.

Common side effects:low blood counts, mouth sores, skin rash/acne, mild nausea, abnormal liver function.


Ara-C, Arabitin, Aracytine, Cytarbel, or Cytosar
Generic Name: Cytosine arabinoside



Mode of Action: Ara-C is a DNA synthesis inhibitor. Its structure is very similar to the nucleotide C, but instead of having a ribose (for RNA) or a deoxyribose (for DNA) sugar, its consists of an arabinose sugar - a 5 carbon sugar that competes for the enzymes in DNA synthesis, but cannot function in DNA or RNA.

Common Side effects: decreased blood counts with risk of infection, bleeding and anemia which may require blood transfusion, nausea and diarrhea, abdominal pains, mouth sores, liver injury (which gets better after the drug is stopped).


For Further Information, see:

Chemotherapy Pages, Imaginis - Breast Cancer information , Prostate Cance, Lung Cancer


Do you have a mother , grandmother, aunt, or friend, who has breast cancer, or is a breast cancer survivor?
The 2003 IUPUI Race for the Cure will take place on Saturday, April 12. Come along and do the Family Walk, or the the 5K walk or run! I will have more details soon, and registration forms, but in the meantime, for more information, see information at the Komen Foundation.

The text of this "What is Biology Good For" exercise is copyrighted under the name of Dr. Kathleen A. Marrs, 1999, 2000, 2001, 2003. There are no restrictions on its use by educators or by non-profit institutions as long as its content not modified, proper copyright acknowledgement is retained, and this statement is not removed.

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Extra Credit Questions: Please answer the following questions on a piece of paper and turn it into me.


1. Aside from Chemotherapy, list at least two other methods available to stop the spread of cancer, breast cancer or otherwise.
2. What is
leukemia and why would it be treated with chemotherapy rather than other methods?
3. Tumors metastisize when they attract new blood vessel growth (angiogenesis) and escape to other parts of the body via the new blood vessel. Why might drugs called
angiogenesis inhibitors be useful in stopping the spread of cancer ?

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