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Bhuvana Ramaswamy, MD


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New Hope For Women Who Are Tamoxifen-Resistant

Up to 40% become resistant, drug developed for other conditions may help

(COLUMBUS, Ohio) October 2012 – Since it was first approved by the FDA in 1977, tamoxifen has become one of the most effective and widely prescribed treatments for breast cancer.  Millions of women have used it, not only as a treatment for breast cancer, but, in some cases, to prevent it from developing in the first place.  And because it is a pill and has few serious side effects, tamoxifen has become a favorite of doctors and patients alike.

“I would say that tamoxifen has been a true breakthrough in cancer therapy,” said Bhuvana Ramaswamy, MD of Ohio State’s James Cancer Hospital.  “It has improved disease-free survival by 50-percent.”

But for some women that protection is only temporary.  “Unfortunately, 30 to 40 percent of patients who take tamoxifen become resistant to it after about five years,” said Ramaswamy.  When they do, it invariably means their cancer will return and, outside of chemotherapy, those patients have very few treatment options.

Now, results of a study conducted by researchers at Ohio State’s Comprehensive Cancer Center may offer new hope.¹  Analyzing over 300 human tumors, researchers here have identified the pathways that certain cancer cells use to render tamoxifen ineffective.  One is called Hhg, nicknamed the “hedgehog pathway”, the other is known as P13K/AKT pathway.

After identifying the pathways these cancer cells use to survive, scientists then subjected them to a new drug and saw some remarkable results.  “The cancer cells died very quickly,” said Dr. Ramaswamy, “the tumor shrank and the healthy cells remained intact.”

What’s more encouraging is that the drug they used, called vismodegib, is already being testing in other cancers and has recently been approved for the treatment of basil cell carcinoma. 

“The fact that this drug has already been tested extensively is huge,” said Sarmila Majumder, PhD of Ohio State’s Comprehensive Cancer Center.  “It’s already gone through phase 1, 2 and 3 trials in other conditions and we already have it here in our clinic.  So, if we see that it may help patients with another type of cancer, we don’t have to repeat those steps and we can save a lot of time,” she said.

“Now it’s a matter of collaborating with the company that makes this drug and with the National Cancer Institutes to bring this to a clinical trial for breast cancer patients,” said Ramaswamy.  Hopefully, that can take place in a matter of months, not years.

The study is published in the journal Cancer Research.

Approximately 230,000 new cases of breast cancer are expected in the United States in 2012, and almost 40,000 Americans will die from the disease. More than two-thirds of breast cancer cases show high levels of the estrogen receptor, which is the primary target of drugs like tamoxifen.

Funding from the NIH/National Cancer Institute (grants CA137567 and CA133250) and a Pelotonia Idea grant supported this research.

Other Ohio State researchers involved in this study were Yuanzhi Lu, Kun-yu Teng, Gerard Nuovo, Xiaobai Li and Charles L. Shapiro.

¹Hedgehog signaling is a novel therapeutic target in tamoxifen resistant breast cancer aberrantly activated by PI3K/AKT pathway, The Journal Cancer Research, August 8, 2012.  Online:  http://cancerres.aacrjournals.org/content/early/2012/08/07/0008-5472.CAN-12-1248.abstract

 

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