drug resistance in ovarian cancer
Researchers at the School of Medicine report that a specific defense mechanism used by the immune system is imitated by cancer cells in order to fight off the effects of cancer drugs like paclitaxel.
The study -- led by Dr. Gil Mor, associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences -- suggests that two proteins, TLR-4 and MyD88, may indicate an increased risk for developing ovarian and other cancers, and could provide clues to a new drug target aimed at reversing chemoresistance to paclitaxel.
Published recently in Cancer Research, the work sheds light on the association between cancer and the active membrane receptor proteins TLR-4 and MyD88. TLR-4 belongs to a family of membrane receptors called Toll-like receptors (TLR) that play a role in the recognition processes of the immune response.
Mor and his colleagues assayed for TLR-4 in samples of ovarian cancer tissues and determined that it is produced in epithelial ovarian cancer cells. The TLR-4 and MyD88 proteins allow cancer cells to respond to bacterial stimuli by producing cytokines that stimulate tumor growth.
"We have also identified a sub-group of ovarian cancer patients who express MyD88 and are paclitaxel resistant," says Mor. "In these patients, instead of inducing tumor death, paclitaxel induces tumor growth."
"We are preparing a clinical trial to validate the expression of MyD88 as a marker for paclitaxel resistance. Preliminary studies indicate this is the case," Mor adds. "Our work provides new insight into a molecular mechanism that links inflammation and the development and progression of ovarian cancer."
Chronic infection and inflammation are considered among the most important factors contributing to cancer development and growth. Individuals with ulcerative colitis, for example, have a 10-fold higher likelihood of developing colorectal cancer. Similarly, ovarian endometriosis, a condition that promotes a pro-inflammatory environment within the ovary on a cyclical basis, predisposes women to specific types of epithelial ovarian cancer. The drug paclitaxel, which is used to treat ovarian and other cancers, interferes with the growth of cancer cells, which are eventually destroyed.
Mor says animal studies have shown that surgical removal of a primary tumor is often followed by rapid growth and spread of previously dormant cancer. These findings may help pave the way to understanding this phenomenon.
Other participants on the study are Dr. Michael G. Kelly, Ayesha B. Alvero, Rui Chen, Dr. Dan-Arin Silasi, Vikki M. Abrahams, Serena Chan, Irene Visintin and Dr. Thomas Rutherford.
T H I S
W E E K ' SS T O R I E S
PBS news anchor elected as trustee
Ceremony formally marks Rose Center opening
New Peabody hall offering high-tech lessons about Earth and space
Scientists believe that green tea may be key to 'Asian paradox'
COMMENCEMENT 2006
University celebrates its 305th graduation
Baccalaureate Address
Honorary Degrees
Other student awards
ENDOWED PROFESSORSHIPS
James Gustave Speth named Sara Shallenberger Brown Professor
James Baron comes to SOM as the William S. Beinecke Professor
New exhibit asks: What did Shakespeare really look like?
Samples from ocean floor at the North Pole yield clues . . .
MEDICAL SCHOOL NEWS
Nation's first manual for treating radiation victims developed
Animals may provide warning of bioterrorist attack, say researchers
Researchers uncovering clues to drug resistance in ovarian cancer
Scientists find way to use intestinal cells to stop . . .
Study: Less-invasive surgery equally effective for infants . . .Scientists unlocking key to molecular basis of debilitating pain . . .
Arts & Ideas festival adds a dash of New Orleans spice
Art & Architecture Library taking up temporary residence on Crown Street
Forum explores governmental budgetary processes in China
Library events celebrate aviator and author Anne Morrow Lindberg
Making the Grade
Uncovering Ingrained Attitudes About Obesity
Nursing School research shows ideas about ideal weight . . .
Rudd Center survey reveals that many people would give up . . .
Artist's exhibit at Slifka Center will examine complexity of faith
Jaroslav Pelikan, renowned scholar of church history
Event will bring bellringers from near and far to the Yale campus
Gigantic balloon creatures to invade Hall of Dinosaurs
Celebrated performer to teach summer flute institute
Drama production will highlight work by New Haven students
Reading aloud
Campus Notes
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