October 24 - 28, 2011
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Improving Workplace Dynamics
- FARE Award Ceremony
- Poster Sessions
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Research Festival Committees
- Past Research Festivals
2011 program
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Acquired resistance to the death-receptor targeted therapies in breast cancer cells
| Monday, October 24, 2011 — Poster Session I | |||
|---|---|---|---|
Noon – 2:00 p.m. |
Natcher Conference Center |
FDA/CBER |
CANCER-21 |
Authors
- L Rivera Rosado
- B Zhang
Abstract
TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis through its death receptors (DRs) 4 and/or 5 expressed on the surface of target cells. The selectivity of TRAIL towards cancer cells has prompted clinical evaluation of recombinant human TRAIL (rhTRAIL) and monoclonal antibodies to DR4 or DR5 for treating various malignancies. However, the utility of these targeted therapies is hindered by the development of resistance in tumor cells. We have previously observed an acquired resistance to rhTRAIL in breast cancer cells. Here we report that breast cancer cells also develop resistance to anti-DR agonistic antibodies after repeated treatments with subtoxic doses of individual antibodies. Interestingly, the cells developed resistance not only to the antibody with which they were treated but also to the complementary antibody and to TRAIL. We also provide evidence that the acquired resistance is associated with alteration in several intracellular signaling molecules.
