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Phenylacetate-bisphosphonate as a new anticancer candidate Breast cancer
represents the 4th most common cause of cancer related death in the US having
claimed the lives of well over 1 million women between 1970 and 1994. High
levels of mortality result from a combination of high incidence and the lack
of options open to those patients who fail first line therapy and develop
metastases. Once metastasis occurs, prognosis and quality of life both
diminish with rapidity. The formation of bony metastases contributes to the
latter through the production of skeletal pain and increased risk of fracture.
A number of bisphosphonates have been developed to tackle this problem. This
class of drugs inhibits osteoclast function and has been extensively developed
for the treatment of osteoporosis. More recently
researchers have demonstrated that bisphosphonates have direct antitumor
effects. In vitro, bisphosphonates inhibit proliferation and induce apoptosis
in cultured human breast cancer cells. In addition, bisphosphonate treatment
interferes with breast cancer cell adhesion to bone matrix, and inhibits cell
migration and invasion. More recently researchers at Novartis have
demonstrated that zoledronic acid, a new generation bisphosphonate with a
heterocyclic imidazole substituent, is also a potent inhibitor of angiogenesis. The aromatic fatty acid phenylacetate (PA) and its analogs have also been investigated with respect to their ability to cause the growth arrest of a variety of neoplasia, including human breast cancer. The effects of these molecules, especially their ability to reduce the proliferation of ER+ breast cancer cells, may in part be due to their potent antiestrogen properties. NaPa also limits the invasiveness of metastatic cancer cell by modifying cell structure and increasing expression of adhesion molecules such as u-PAR and LFA-1. Now researchers based in France have taken a step forward by evaluating the antitumor effects of a new bisphosphonate, the phenylacetate-bisphosphonate (PaBp), on human breast cancer cell lines. The use of bisphosphonates as a treatment of cancer is sure to receive growing information and further study of PaBp, a molecule that combines two therapeutically active groups to offer cytostatic, cytotoxic, proapoptotic and antiangiogenic activity is of considerable interest. Entry date March, 2003 Adapted from Sebbah-Louriki et al, Anticancer Res 2002 Nov-Dec;22(6C):3925-31 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.
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