Download Her-2 study questions 2005

Biology 207: STUDY QUESTIONS FOR HER-2: THE MAKING OF
HERCEPTIN, A REVOLUTIONARY TREATMENT FOR BREAST CANCER.
Reading available in bookstore or on reserve (book or electronic reserve), Milne
library:
Bazell, R. (1998) Her-2: The Making of Herceptin, a Revolutionary Treatment for
Breast Cancer. Random House, New York, NY.
We will be reading and discussing Her-2 over the course of the next couple of
weeks. Her-2/neu is a protein receptor found on some cells, often those in the epithelial
cells of the breast. When mutated, the her-2/neu gene is an oncogene encoding a protein
that pushes cells toward cancer. Patients with mutated her-2 on their breast cells often
have very aggressive forms of cancer.
Herceptin is a drug designed to inactivate the mutant receptor in breast cancer
patients that express her-2. It is essentially an antibody (a protein that binds another
protein or antigen) and is one of the first drugs of its type to be made available for the
treatment of cancer. Unlike traditional chemotherapeutic drugs which often affect both
normal and cancer cells causing toxic side effects, herceptin specifically attacks the breast
cancer cells that are expressing her-2. Thus, herceptin/her-2 serves as a model of the
types of targeted cancer therapies that we hope will be more available in the future.
Key questions to think about as you read this book:
1. How is breast cancer diagnosed?
2. What are the treatment options available?
*3. What combinations of drugs are used in chemotherapy or adjuvant chemotherapy for
breast cancer? Provide at least three examples of chemotherapeutic drugs used in the
treatment of breast cancer and give their mode of action.
4. What are the side effects/drawbacks of traditional treatments?
5. How was the role of her-2 discovered?
*6. What is the biological basis for herceptin as a treatment for breast cancer?
7. What are the steps involved in taking an idea for an anti-cancer drug all the way
through the FDA approval process?
8. Why can’t herceptin therapy help all breast cancer patients?
1
9. What is the difference between a biotechnology company (like Genentech) and a
pharmaceutical company?
*10. What are clinical trials? How are clinical trials executed? What is the difference
between phase I, II and III trials?
11. What are some of the organizations that breast cancer patients can turn to for support
and/or advocacy?
*12. What are some of the ethical issues involved in the testing and distribution of
promising new cancer drugs?
Alternate final homework assignment (in case you can’t get the drug design software
to work), 10 points. Type or print your answers to questions #1-12 and hand in on or
before the final exam.
Definitions:
adjuvant chemotherapy: When chemotherapy is combined with another medical
treatment.
adriamycin (doxorubicin): Chemotherapeutic drug that interferes with DNA synthesis.
Undesirable side effects include heart muscle damage, in addition to nausea, hair loss and
bone marrow destruction.
antibodies: Proteins that bind specifically to other molecules called antigens.
biopsy: Surgical removal of tissue for examination of possible tumors.
CAF therapy: Cytoxan-adriamycin-5-fluorouracil; A combination chemotherapy.
cisplatin: Chemotherapeutic drug used for treating ovarian and sometimes breast cancer.
Tested in combination with her-2 antibody. Reacts with DNA to induce damage.
CMF cocktail: Cytoxan-methotrexate-fluorouracil; A combination chemotherapy.
Compassionate access: Making expensive drugs available to more patients.
cytoxan: Chemotherapeutic drug that interferes with DNA synthesis.
double-blind trial: When the patient and the experimenter are both kept unaware of
whether a patient is receiving a drug or a placebo in a clinical trial.
epidermal growth factor (EGF): A small molecule that stimulates growth by binding to
a receptor.
ER: Estrogen receptor. The protein on the surface of cells that binds estrogen, so that it
can start to stimulate cell growth.
estrogen: A female sex hormone; stimulates growth of breast cells.
FDA: U.S. Food and Drug Association. Agency responsible for establishing the
effectiveness of a drug before it can be made available for non-experimental treatments.
fluorouracil (5-fluorouracil): Chemotherapeutic drug. Is similar to a nucleotide
(building block of DNA) and thus interferes with DNA synthesis.
gene splicing: The same as genetic engineering or cloning. Linking together two
unrelated genes in a test tube. Enables large amounts of the gene or the protein encoded
by the gene to be made. Used in the development of herceptin.
2
her-2/neu: Protein receptor that binds a growth factor.
herceptin: An antibody against the her-2 receptor that has cancer chemotherapeutic
properties.
interferons: Proteins that act as growth stimulatory or inhibitory factors of cells in the
immune system.
lumpectomy: Surgical removal of the tumor in a breast.
mastectomy: Surgical removal of the breast.
menopause: When women no longer menstruate.
methotrexate: Chemotherapeutic drug. Interferes with DNA synthesis.
oncology: The study of cancer.
phase I trials: Small initial trial of less than 50 critically ill patients to test for toxicity of
a new drug.
phase II trials: Small test of less than 50 critically ill patients to determine a drug’s
possible effectiveness in treatment, once its possible toxic effects are known.
phase III trials: Large test of hundreds to thousands of patients to establish whether
drug works well enough to seek FDA approval to bring it to market.
placebo: A “sugar-pill” used for comparison in testing the efficacy of a new drug in
clinical trials.
raloxifene: An estrogen blocker similar to tamoxifen. May have fewer side effects than
tamoxifen.
steroid: Molecules such as estrogen, testosterone and cholesterol. Many are hormones
which bind to receptor proteins on the cell surface triggering growth.
tamoxifen: A synthetic non-steroid compound that has some hormone-like effects and
can block the action of estrogen. Approved as a preventative drug for women at risk for
breast cancer.
taxol: Chemotherapeutic drug for ovarian cancer and breast cancer from the bark of the
Pacific yew tree. Affects cell division by interfering with microtubules, protein rods that
help move the chromosomes in mitosis.
taxotere: Synthetic version of taxol.
TNF: Tumor necrosis factor. A growth factor that acts on cells of the immune system.
3