The PJS Gene & Endometrial Cancer in Mice

This isn't about PJS people, but genetically engineered mice!

Yet it's interesting because we know that we're at increased risk of
reproductive tract tumors and the authors explore some possibilities about why &
how. Also, they used rapalogs (like RAD001 and Rapamycin that we've discussed
here) to reduce endometrial cancer progression and shrink tumors in the
affected mice.

It's interesting to consider. Perhaps someday research and trials will help
us PJS folks, not just the PJS mice. :)

Love,
Stephanie
***********



Single gene mutation induces endometrial cancer, researchers find

DALLAS - Feb. 10, 2010 - A mutation in a single gene can cause endometrial
cancer that is responsive to a specific drug therapy, researchers at UT
Southwestern Medical Center have found in an animal study.

The finding suggests that eventually it might be possible to screen women
with endometrial cancer to see if they have that mutation and use the drug as
targeted therapy, the researchers said.

“Our data suggest that deficiency of this gene can indicate both how
aggressive an endometrial tumor will be and how well it might respond to a
specific class of drugs,” said Dr. Diego Castrillon, assistant professor of
pathology at UT Southwestern and senior author of the paper, which appears in the
March/April issue of Disease Models and Mechanisms.

“Some early clinical trials have shown that about one-fifth of women with
endometrial cancers respond to a group of drugs called 'rapalogs,'” Dr.
Castrillon said. “Unfortunately, it is not currently possible to predict which
women these are.”

Endometrial cancer affects the lining of the uterus. This cancer is the
most common cancer of the female reproductive tract and is usually detected
when a woman complains of excessive bleeding. About one-third of ovarian cancer
cases are believed to begin as endometrial cancer, Dr. Castrillon said. The
median survival of women with advanced endometrial cancer is one year.

The researchers focused the gene Lkb1, which is known to suppress other
types of cancers. Mutations in Lkb1 disrupt its “braking” action on cancer and
contribute to the disease in lungs, skin and other tissues.

In the current study, the researchers genetically engineered mice to
inactive Lkb1 only in the endometrium. Without Lkb1, the entire endometrium became
cancerous early and rapidly, they found.

The researchers found that treating the cancerous mice with the anti-cancer
drug rapamycin slowed the progression of the cancers and dramatically
shrank existing tumors.

“We hope that someday a test based on this gene or others like it might
pinpoint which women would respond best to treatment with 'rapalogs,'” Dr.
Castrillon said. “Such personalized medicine could spare other women from
unnecessary chemotherapy if their tumors are unresponsive to the drugs.”

Other UT Southwestern researchers participating in the study were graduate
students Cristina Contreras and Esra Akbay; senior research scientist Teresa
Gallardo; research assistant Marshall Haynie; Dr. Masaya Takahashi,
associate professor in UT Southwestern's Advanced Imaging Research Center; and Dr.
Osamu Togao, postdoctoral research fellow in the Advanced Imaging Research
Center.

Researchers at Harvard Medical School also participated in the study.

The research was supported by the National Cancer Institute, a
Translational Science Award from the Sidney Kimmel Foundation for Cancer Research, the
American Cancer Society, and the Harold C. Simmons Comprehensive Cancer
Center at UT Southwestern.