Cancer cells avoid apoptosis by a variety of genetic and epigenetic mechanisms. We are investigating the induction of apoptosis by activation of death receptors for the ligand tumor necrosis factor-related apoptosis inducing ligand (TRAIL) in breast and ovarian cancer cells. Previously, we have shown that many breast and ovarian cancer cell lines are resistant to the induction of apoptosis by TRAIL, the ligand for the death receptors DR4 and DR5. We have demonstrated that resistance to TRAIL-induced apoptosis can be overcome by co-incubation of the cells with chemotherapeutic agents, semi-synthetic retinoids (such as 4HPR), or molecularly targeted agents (such as anti-ErbB-2 antibodies). Our current work utilizes biochemical and genetic approaches to identify mechanisms that regulate the induction of death by TRAIL ligand in breast and ovarian cancer cells. Recently, we have shown that TRAIL selectively kills triple-negative breast cancer cells that have mesenchymal features. Ongoing work is investigating the molecular basis for this selectivity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC007263-16
Application #
7735380
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2008
Total Cost
$433,310
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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