Gleevec: A Possible Therapeutic Drug for Notch and/or c-Myc positive Breast Cancer

​​​​​​​An article published in Experimental Biology and Medicine (Volume 242, Issue 1, January, 2017) showed that a imatinib mesylate (Gleevec), a drug approved by the FDA for the treatment of leukemia and other blood disorders, prevents mammary tumor growth in mice. This study, led by Dr. Ahmed Raafat from the National Cancer Institute at the National Institutes of Health in Bethesda, MD, showed that Gleevac treatment inhibits signaling pathways that drive tumor growth.  

Breast cancer is the most common female cancer in the United States, the second leading cause of cancer death after lung cancer, and the main cause of death in women aged 20 to 59. In 2010, approximately 207,000 American women were diagnosed with breast cancer and despite early detection and improved treatments almost 40,000 will die of it.

Cancer research aims at a better understanding of normal mammary development and the etiology of breast cancer. Identifying and dissecting signaling pathways that are involved in tumor initiation, progression and metastasis provides a basis for the development and testing of novel therapies. Inappropriate Notch signaling occurs in numerous human cancers, including breast cancer. The MYC gene is a direct transcriptional target of Notch.  Consistent with this observation, Notch1 and MYC expression was shown to be positively correlated in 38% of human breast cancer.

In the current study by Dr. Raafat and colleagues, using in vitro soft agar assays, tyrosine-kinase inhibitors blocked the growth of breast cancer cells expressing Notch or Myc. Treatment of mice bearing Notch4/Int3 or HC11-Myc mammary tumors also resulted in tumor regression. Tyrosine-kinase inhibitors such as Gleevec induce Notch proteolysis through phosphorylation leading to Notch’s ubiquitination and proteolysis by the proteasome. These researchers hypothesize that tyrosine-kinase inhibitors induce Myc proteolysis in the same way. Dr. Raafat said, “these results indicate that tyrosine kinase inhibitors (i.e. Gleevec) may be effective in the treatment of triple negative breast cancers that are c-Myc and/or Notch positive”.

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said, “this exciting study further elucidated the molecular basis of Gleevec’s inhibition of Notch signaling and suggests that this drug should be considered as a potential therapeutic for Notch4 and/or c-Myc positive breast cancer.”

About Experimental Biology and Medicine

Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal please visit http://ebm.sagepub.com/.

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Source: Experimental Biology and Medicine