vitA and D inhibits breast cancer cells....

[RobinP]

Found the the following article interesting concerning VitD and hormone like vitA. I already take vit D for bone health; now maybe I will try vitA too.




Michael P. DiGiovanna, MD, PhD [img]images/spacer.gif[/img] [img]images/spacer.gif[/img]
Associate Professor of Medicine and Pharmacology
Co-Director, Breast Cancer Research Program, Yale Cancer Center
Yale University School of Medicine
New Haven, CT

2005-2006 BCRF Project:
(made possible by generous support from Roche) The growth factor receptor HER2 (also known as HER-2/neu and ErbB-2) is overproduced in about 25%-30% of all breast cancers. Women whose breast tumors over-express HER2 often have aggressive disease and a prognosis that is worse than that for patients with normal HER2 levels. Over-expression of HER2 also appears to alter an individual’s response to treatment. For example, patients whose tumors over-express HER2 often do not benefit from hormonal (anti-estrogen) therapy such as tamoxifen, but they often respond well to the chemotherapy drug doxorubicin (Adriamycin). In addition, the novel anti-cancer drug Herceptin specifically targets HER2. While treatment with Herceptin is more likely to be successful as HER2 levels rise, even among tumors with the highest levels of over-expression, it is not known why only a small proportion responds to the drug.

Dr. DiGiovanna’s work suggests one possible explanation for this phenomenon. As a growth factor receptor, HER2 must be switched on, or "activated," to transmit its growth signals. Thus, HER2 can exist in an "on" or "off" position, much like a light switch. While other tests measure the level of HER2 overexpression, the test developed by the Yale team measures the activity of HER2. They have found that it is only the tumors with activated HER2 that are aggressive and are associated with a poorer prognosis; tumors that have HER2 in a non-activated state have the same clinical behavior as less aggressive tumors that don’t express HER2 at all.

In the year ahead, the investigators will continue these studies. One of their major goals is to determine how ACTIVATED HER2 impacts response to Herceptin and other chemotherapies. Their other goal is to study the effects of combining agents such as Herceptin and tamoxifen with each other and with novel relatively non-toxic biological therapies. They propose to study these drugs in combination with novel therapeutics that inhibit two other growth-promoting pathways (known as IGF-I and IL6), and explore the use of derivatives of the hormone-like Vitamin A (retinoids) and Vitamin D, which have natural abilities to inhibit the growth of breast cancer cells. They hope that combinations of such "non-toxic" biological therapies may one day replace conventional chemotherapy in the treatment of breast cancer.

During the past two years, the researchers have used all-trans retinoic acid, a derivative of vitamin A, to advance their studies. They have seen that all-trans retinoic acid (atRA) synergistically inhibits the growth of breast cancer cells when used in combination with Herceptin or Tamoxifen, and in combination with Herceptin causes breast cancer cells to undergo cell death, making this an attractive combination to test in breast cancer patients. Drugs that inhibit a growth factor receptor called IGF-I receptor enhanced the effect of Herceptin on HER2-over-expressing cells, and in cells that have low levels of HER2 and don’t normally respond to Herceptin, the Herceptin enhanced the ability of the IGF-I receptor inhibitors to block growth.

Bio:
Dr. DiGiovanna is a native of Long Island, NY, who graduated from Cornell University in 1984 with a B.A. and a double major in the fields of biochemistry and music. He attended Yale Univeristy from 1984 through 1990 where he was earned the MD and PhD degrees, with his PhD in Pharmacology. He continued his post-graduate training at Yale, performing internship and residency in Internal Medicine, a laboratory research post-doctoral fellowship, and a clinical fellowship in Medical Oncology. He is currently an attending physician in Medical Oncology and Associate Professor of Medicine (Medical Oncology) and Pharmacology at Yale University. Dr. DiGiovanna is Co-Director of the Yale Cancer Center's Breast Cancer Research Program.

Dr. DiGiovanna's clinical specialty is breast cancer and his laboratory research is also focused on breast cancer. His research has explored signaling by growth factor receptors in the EGF receptor and HER-2/neu/ErbB-2 family, as that relates to the clinical behavior of breast cancers and response to individual therapies. The lab is also exploring the therapeutic potential of using inhibitors of these growth factor receptors in combination with drugs that target other biological growth pathways, including the estrogen receptor, retinoid (Vitamin A-like) receptors, and insulin-like growth factor.