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Potential new drug effective in breast cancer and melanoma resistant to targeted therapies
Date:10/20/2013

BOSTON LEE011, a small-molecule inhibitor of cyclin-dependent kinases (CDK) 4/6 being developed by Novartis Oncology, showed promising results in drug-resistant melanoma and drug-resistant breast cancer when tested in combination with other targeted therapies, and based on these preclinical results, several phase I clinical trials were launched recently, according to results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held October 19-23.

In many cancers, a tumor suppressor protein called retinoblastoma is deactivated because of an increase in the activity of the proteins CDK 4 and 6. This results in unchecked cell proliferation. The activity of CDK4/6 is regulated by cyclin D, whose expression is increased by activation of BRAF and PIK3CA, which are implicated in some melanomas and breast cancers, respectively. Drugs targeting BRAF and PIK3CA have had success, but most treated cancers subsequently develop resistance to these drugs.

"Chemistry optimization has led to the discovery of LEE011, which, to our knowledge, is the most selective CDK4/6 inhibitor to date," said William Sellers, M.D., vice president and global head of oncology at the Novartis Institutes for Biomedical Research in Cambridge, Mass. "Utilizing the latest cancer genomics data and our knowledge of the role of CDK4/6 activity in the growth of tumor cells, we have identified unique indications and combinations of drugs with LEE011, in which LEE011 demonstrates a robust antitumor activity.

"One of the most notable findings is that, when paired with other targeted agents, LEE011 is often able to prevent the emergence of resistance to the partner compound that would otherwise arise when the partner compound is dosed alone."

Based on the results from preclinical experiments, Novartis has initiated multiple phase I trials in adult cancers, and a phase I trial in pediatric cancers is ongoing. "Preli
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Contact: Lauren Riley
lauren.riley@aacr.org
215-446-7155
American Association for Cancer Research
Source:Eurekalert

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