WP760 for Malignant Melanoma Therapy

描述（由申请人提供）：皮肤癌是美国最常见的癌症，黑色素瘤是皮肤癌中最恶性的。 黑色素瘤在美国的发病率比任何其他癌症都增长得更快。 转移性黑色素瘤患者5年后的生存率<5%，黑色素瘤最近取代白血病，导致工作场所损失更多时间。 目前还没有获得批准的转移性黑色素瘤治疗方法达到超过20%的反应率。 德克萨斯大学医学博士安德森癌症中心目前管理着美国最多的黑色素瘤患者。 与Callisto制药公司一起，该公司开发小分子抗癌药物，我们建议探索最近发现的新型抗黑色素瘤药物WP 760的潜在开发。 WP 760是一种双嵌入DNA结合药物，基于NCI体外抗肿瘤筛选的初步数据，其已显示出对黑素瘤细胞的显著选择性。 使用比较程序，一种比较药物特征的算法，NCI的研究人员发现WP 760对黑色素瘤具有高度选择性的活性，这是明显独特的，与它所比较的所有80，000种其他癌症药物不同。 在这个I期FLAIR STTR应用中，我们建议进一步评估WP 760作为治疗黑色素瘤药物的潜力，目的是进入黑色素瘤临床试验并最终商业化。 我们提出优化生产化学和制剂、啮齿动物中的药代动力学和毒性性能、人黑素瘤与其他肿瘤对WP 760体外生长抑制的敏感性，以及最终使用全身施用WP 760在人黑素瘤异种移植小鼠模型中测试功效以接近人类用途。 成功完成这些目标后，将提交II期STTR进行最终临床前研究，从而获得IND申请和人体临床试验测试。

DESCRIPTION (provided by applicant): Skin cancer is the most prevalent cancer in the USA, and melanoma is the most malignant of skin cancers. The incidence of melanoma in the USA is increasing more rapidly than for any other cancer. Patients with metastatic melanoma have <5% survival after 5 years, and melanoma recently replaced leukemia as responsible for more lost hours in the work place. Currently there are no approved therapies for metastatic melanoma that achieve more than a 20% response rate. The University of Texas, M.D. Anderson Cancer Center currently manages the largest number of melanoma patients in the US. Together with Callisto Pharmaceuticals Inc., which develops small-molecule anticancer drugs, we propose to explore the potential development of a recently discovered novel antimelanoma drug, WP760. WP760, is a bis-intercalating DNA binding drug which has demonstrated remarkable selectivity towards melanoma cells, based on preliminary data from the NCI in vitro anti-tumor screen. Using the Compare Program, an algorithm that compares drug profiles, researchers at the NCI found WP760 to have a highly selective activity against melanoma that was distinctly unique and different from all of the 80,000 other cancer drugs to which it was compared. In this Phase I FLAIR STTR application, we propose to further evaluate WP760's potential as a drug to treat melanoma, with the intent of moving to clinical trials in melanoma and eventual commercialization. We propose optimization of production chemistry and formulation, performance of pharmocokinetics and toxicity in rodents, sensitivity of human melanoma vs. other tumors to growth inhibition by WP760 in vitro, and finally testing of efficacy in a human melanoma xenograft mouse model using systemic administration of WP760 to approach the human use. Successful completion of these objectives will then be followed by a Phase II STTR submission for final preclinical studies, leading to an IND application and clinical trial testing in humans.