IGF::OT::IGF PHASE IB 9CUAB30 IN EARLY STAGE BREAST CANCER TO EVALUATE BIOLOGIC EFFECT

以维甲酸受体（RARs）为靶点的类维生素a和以类维甲酸X受体（RXRs）为靶点的类维生素a代表了两类具有有效预防乳腺癌能力的潜在药物，并已被广泛研究。9cUAB30是一种新型的rxr选择性类维生素a，是9顺式UAB30的构象约束类似物。在动物模型中，9cUAB30已被证明可以预防er阳性和er阴性的乳腺癌，其效力与目标蛋白相似。此外，仅在治疗7天后，细胞增殖和凋亡就出现了调节。重要的是，基因表达阵列分析已被用于证明9cUAB30不是肝脏中的激动剂，这是组织选择性类维生素a所需的标志。

Retinoids, which target the retinoic acid receptors (RARs), and rexinoids, which target the retinoid X receptors (RXRs), represent two classes of potential drugs with potent capacity to prevent breast cancers and have been studied extensively. 9cUAB30 is a novel RXR-selective retinoid, which is a conformationally constrained analog of 9 cis UAB30. In animal models 9cUAB30 has been shown to prevent both ER-positive and ER-negative mammary cancers with similar potency to Targretin. Additionally, modulation of proliferation and apoptosis was seen after only 7 days of treatment. Importantly gene expression array profiling has been used to demonstrate that 9cUAB30 is not an agonist in liver, which is the desired hallmark of a tissue-selective rexinoid. This single arm phase IB study is designed to determine if 9cUAB30 at the selected dose modifies breast tissue biomarkers. Therefore, this statement of work outlines the requirements for the study, including (but not limited to) participant accrual, agent administration and patient follow-up as well as associated biomarker analyses. This statement of work includes protocol activities to screen 80 participants and enroll 40 on trial stratified by ER status of the tumor as well as perform biomarkers on matched control cases.