Her-2: Summary of Chapters 1-6

Biology 207 Biology of Cancer April 19, 2002

The PATIENTS

Anne McNamara Married, one child Breast cancer first diagnosed 1978, age 32 Risk factor: Previous history of fibrocystic disease Surgical option she chose: biopsy, if positive, mastectomy No chemotherapy or radiation therapy recommended by doctor. Patient thought she should have chemotherapy. Reconstructive surgery Recurrance of cancer along mastectomy scar in 1982 Biopsy by surgeon--> malignant Oncologist prescribed combination chemotherapy: CMF, cytoxan, methotrexate, fluorouracil. Sessions every 2-3 weeks for 6 months. Side effects of CMF: nausea, thinning hair, premature menopause Also put on tamoxifen (anti-estrogen) therapy Second recurrance of breast cancer After biopsy to show it was malignant had 6 weeks of radiation therapy Side effects of radiation: nausea, swelling, skin redness Lifestyle changes post-breast cancer--priorities, travelling, family time, planning for death

Barbara Bradfield 1990--48 yr old woman Detected lump under her arm, another found in her breast First diagnosed as stage II-III inflamatory breast cancer No family history of breast cancer Test for cancer spread to bone marrow--awful experience Sought second opinon Six months chemotherapy to shrink tumor, mastectomy, more chemotherapy, then radiation therapy. Investigated alternative therapies Aug. 1992--Recurrance of breast cancer--felt lump on neck; also had metastasized to lungs. Was refered to Dennis Slamon’s Phase I trial of the her-2 antibody/cisplatin just as she was planning to go to a Mexican clinic for alternative treatments. First positive response to the antibody treatment; only survivor of her group of 15 in phase I trials.

THE SCIENTISTS/PHYSICIANS (+many coworkers) Robert Weinberg MIT first discovered Her-2 (called in neu) oncogene; known for studies of Ras oncogene and the Rb tumor suppressor Axel Ullrich Genentech second to discover Her-2, first to clone it and study it in detail Dennis Slamon UCLA first showed Her-2 expressed in breast and ovarian tumors; staked career on Her-2 antibody therapy; more aggressive breast tumors ass. with Her-2 expression

THE “CURE”

Her-2/neu: A protein receptor on the cell surface that binds a particular growth factor.

Her-2 antibody (herceptin): Antibodies are proteins that bind other specific proteins (called antigens). The Her-2 antibody binds the Her-2 receptor on the surface of cells and blocks growth factor binding.

The science behind the treatment:

--genetic engineering (cloning) was used to make enough of the Her-2 protein to study it and to use for making antibodies. --type of antibody = monoclonal, meaning all the antibodies recognize the same region on the protein. --a mouse antibody (mouse monoclonal) was made first, but couldn’t be used in the clinical trials because it might cause an allergic response in humans. --”humanizing” involves genetic engineering of the mouse antibody, to make it more like the human. --Phase I clinical trials: Small intial test of less than 50 critically ill patients to test for toxicity of drug.

The $ behind the treatment:

Genentech The upstart biotech company. Early studies on Her- 2 antibody. Roche (Hoffman-LaRoche) Big pharmaceutical company. Bought Genentech, midway through development of Her-2 antibody. Revlon/Lilly Tartikoff Dennis Slamon’s support