Disease relevance of Arzoxifene

• Accordingly, arzoxifene 20 mg/d was selected for further study in patients with breast cancer [1].
• Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma [2].
• At study termination, body weights for arzoxifene groups were 16-17% lower than OVX control, which was caused by mainly reduced gain of fat mass [3].
• We performed a multi-institutional evaluation of arzoxifene in women with newly diagnosed ductal carcinoma in situ or T1/T2 invasive cancer [4].
• OBJECTIVES: The goal of this study was to determine response rate and evaluate toxicity of LY353381 (arzoxifene) in patients with recurrent or advanced endometrial cancer (EC) [5].

High impact information on Arzoxifene

• The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268 cooperate to promote transforming growth factor beta-dependent apoptosis in breast cancer [6].
• Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer [1].
• Arzoxifene, a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer [2].
• Histology of the uterine endometrium showed that cell heights from both doses of arzoxifene were not significantly different from OVX controls [3].
• Arzoxifene maintained bone formation indices at sham levels and preserved trabecular number above OVX controls [3].

Chemical compound and disease context of Arzoxifene

• Here we study arzoxifene, a short-acting selective estrogen receptor modulator, for its potential to inhibit repopulation in estrogen-dependent human breast cancer MCF-7 xenografts between courses of chemotherapy [7].
• EXPERIMENTAL DESIGN: We have tested the benzothiophene derivatives, arzoxifene (Arzox; LY353381) and LY117018 in two models of Tam-stimulated tumor growth derived from either MCF-7 (M. M. Gottardis and V. C. Jordan, Cancer Res., 48: 5183-5187, 1988) or T47D (J. MacGregor Schafer et al., Clin. Cancer Res., 6: 4373-4380, 2000) breast cancer cells [8].
• Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268 [9].
• Selective estrogen receptor modulators (SERMs) have shown the ability to prevent (GTx-006 [acapodene]) and treat (GTx-006 and arzoxifene) prostate cancer, suggesting that they may be used in prostate cancer chemoprevention [10].

Biological context of Arzoxifene

• Arzoxifene decreased cell proliferation in xenografts [7].
• Effects of oral estrogen, raloxifene and arzoxifene on gene expression in serotonin neurons of macaques [11].
• METHODS: Two phase I studies were conducted to evaluate the safety and pharmacokinetics of single and multiple doses of arzoxifene [12].

Anatomical context of Arzoxifene

• Uteri wet weight from arzoxifene animals was 38-40% of sham compared with OVX rats, which were 29% of sham [3].
• Histomorphometry of the PTM showed that arzoxifene prevented bone loss by reducing osteoclast number in OVX rats [3].
• Compression testing of the vertebra and three-point bending testing of femoral shaft showed that strength and toughness were higher for arzoxifene-treated animals compared with OVX animals [3].
• A new MCF-7 breast cancer cell line resistant to the arzoxifene metabolite desmethylarzoxifene [13].

Associations of Arzoxifene with other chemical compounds

• PURPOSE: Arzoxifene, a new selective estrogen receptor modulator with strong breast antiestrogen activity and absence of uterine agonist activity, was explored as a potential chemoprevention agent [4].
• Paclitaxel or 5-FU alone had minor effects to delay the appearance of xenografts whereas arzoxifene alone caused longer delay [7].

Gene context of Arzoxifene

• Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer [14].
• Northern analysis revealed that arzoxifene exerts a statistically significant inhibition of pS2 and progesterone receptor B mRNA expression [15].
• This suggests that raloxifene and arzoxifene are agonists at ER beta in the context of the serotonin neuron [11].

Analytical, diagnostic and therapeutic context of Arzoxifene

• CONCLUSIONS: Arzoxifene and 4OHT can inhibit specifically the repopulation of ER+ breast cancer cells between courses of chemotherapy [16].
• However, decreases in proliferation indices for arzoxifene were not statistically different from placebo, perhaps due to a confounding effect of stopping hormone replacement therapy before entry [4].
• The benzothiophene selective estrogen receptor modulators (SERMs), raloxifene and arzoxifene, in the clinic or clinical trials for treatment of breast cancer and postmenopausal symptoms, are highly susceptible to oxidative metabolism and formation of electrophilic metabolites [17].

References