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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: John O'Neill who wrote (19386)	4/21/1998 8:07:00 PM
From: Hippieslayer	Read Replies (1) \| Respond to of 32384

i believe CBS evening news will have a special on cancer tonite.

To: John O'Neill who wrote (19386)	4/22/1998 6:56:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

JO, Using Evista to treat breast cancer should not come as a surprise. In fact that is precisely what the LGND/LLY research program targets (although the actual compounds may be second generation SERMs and second generation Rexinoids). I did see C-SPAN coverage yesterday as well as CNN. I expect coverage to continue to be intense, especially since there will be several reports at ASCO next month on Evista and breast cancer prevention. Thus, it's probably time to do another conceptual review. ZEN's Tamoxifen has been approved for treating breast cancer and AHP's Premarin has been approved hormone replacement treatment (HRT). Both drugs target the estrogen receptor. Premarin has been shown to offer several benefits including strengthening bones and protecting the heart. It has also been shown to increase the risk for breast cancer as well as uterine cancer. Tamoxifen has been called an anti-estrogen because it can block estrogen from binding to its receptor. It was approved for treating breast cancer, but the recent trial tested its ability for preventing breast cancer. It was shown to be effective (reduces incidence by 45% in high risk patients), but had significant side effects (uterine cancer and blood clots), which affect a significant number of patients. Evista is another SERM. It has been approved for the prevention of osteoporosis and the upcoming presentation will show that in some cases, it too can prevent breast cancer (at rates of 58% and 74%), It may not have as big of a risk at causing uterine cancer, but it also causes blood clots. Several companies are working on additional SERMs. PFE's most advanced compound is Droloxifene. It was initially in trials for treating breast cancer. Its efficacy was about the same as Tamoxifen, so PFE just switched it to a trial for the prevention of breast cancer. It is also in trails for prevention of osteoporosis as is another PFE compound identified by LGND (CP-366,156) and an AHP compound, TSE424, also identified by LGND. Thus there are several SERMs in the clinic (SBH has Idioxifene), most of which are being tested for prevention of osteoporosis, but also could have breast cancer prevention and treatment properties. In animals Targretin is similar to Tamoxifen for breast cancer prevention and superior for breast cancer treatment. Moreover, it synergizes with Tamoxifen for both applications. Thus Targretin could be used as monotherapy as well as combination therapy. It is currently in clinical trials for both applications for treating breast cancer (in Phase II trials in combination with Tamoxifen and in Phase II/III trials for monotherapy). It is likely that it will also synergize with the other SERMs in the clinic. I'm not sure what SERM-3 is, but suspect that it is a third generation SERM of LLY (with Evista being considered a second generation SERM and Tamoxifen being a first generation SERM).

To: John O'Neill who wrote (19386)	4/22/1998 2:06:00 PM
From: Henry Niman	Respond to of 32384

This may be why Targretin works for treating and preventing diabetes and breast cancer: Wednesday April 22 1:09 PM EDT Insulin, Estrogen Linked With Breast Cancer NEW YORK (Reuters) -- An interaction between the hormones estrogen and insulin may encourage the growth and proliferation of breast cancer cells, a finding that may help explain why diabetes is more common in women with breast cancer, according to a University of Texas-Houston researcher. "What we have found is that the estrogenic influence on breast cancer cells appears to modulate their responses to insulin," said Dr. Victoria Knutson in an interview with Reuters. "That is, when breast cancer cells are chronically bathed with estrogen as occurs in a premenopausal women, the breast cancer cells are more susceptible and more sensitive to insulin, which stimulates the proliferative response of the cells," said Knutson, who presented her findings at the Experimental Biology '98 conference in San Francisco, California, on Tuesday. The researchers found that in the presence of insulin alone, the number of insulin receptors on the surface of breast cancer cells decreased, a normal response. But when bathed in a solution of both insulin and estrogen, the number of insulin receptors on the cell surface remained the same, and the number of estrogen receptors increased by 12 times. This is a "formula for increased tumor growth and proliferation," according to an abstract from the meeting. "The ramifications have really already been noted by epidemiologists who found that in women with breast cancer there was a higher incidence of diabetes and conversely in women with diabetes there was a higher incidence of breast cancer," she said. It's possible that women who have a family history of breast cancer may be at greater risk for developing diabetes, or women with a family history of diabetes may be at greater risk for breast cancer, Knutson said. "I am not aware of what is cause and what is effect," she said. "What happens first, the diabetes or the breast cancer? It may be just a genetic predisposition to either or both."