Phase II Clinical Trial Utilizing Lithium for Patients with Neuroendocrine Tumors

描述(申请人提供)：神经内分泌(NE)肿瘤，如类癌、胰岛细胞瘤和甲状腺髓样癌是孤立肝转移的第二大常见原因。由于荷尔蒙分泌过多，这些肿瘤常常会引起衰弱症状。除了手术外，对于转移性NE肿瘤患者可用的治疗和姑息治疗方法有限，强调了开发其他形式治疗的必要性。在这项提案中，我们将提供数据说明GSK3B抑制可能是治疗NE肿瘤的可行策略。此外，我们将展示有效的GSK3B抑制剂氯化锂，抑制NE肿瘤的增殖和激素的产生。因此，我们建议进行一项II期临床试验，以确定锂是否为NE肿瘤患者的潜在治疗方法。本研究的主要目的是评估锂治疗NE肿瘤患者的有效率。第二个终点是：1)接受锂治疗的NE肿瘤患者的无进展和总存活率；2)锂对NE肿瘤特异性肿瘤标志物的影响；3)锂在这一患者群体中的毒性和耐受性；4)接受锂治疗的NE肿瘤患者的生活质量；5)GSK3B信号通路成员在锂治疗前和治疗期间在参加临床研究的患者的NE肿瘤样本中的表达。综上所述，这些研究是我们设计和开发治疗和缓解不能切除的转移性NE肿瘤患者的新方法的长期目标的一部分。神经内分泌肿瘤，如类癌、胰岛细胞瘤和甲状腺髓样癌是孤立肝转移的第二大常见原因。由于荷尔蒙分泌过多，这些肿瘤常常会引起衰弱症状。除了手术外，对于转移性NE肿瘤患者可用的治疗和姑息治疗方法有限，强调了开发其他形式治疗的必要性。

DESCRIPTION (provided by applicant): Neuroendocrine (NE) tumors such as carcinoid, islet cell tumors, and medullary thyroid cancer are the second most common cause of isolated hepatic metastases. These tumors often cause debilitating symptoms due to excessive hormonal secretion. Besides surgery, there are limited curative and palliative treatments available to patients with metastatic NE tumors, emphasizing the need for development of other forms of therapy. In this proposal, we will present data illustrating that GSK3B inhibition may be a viable strategy for the treatment of NE tumors. Furthermore, we will show that the potent GSK3B inhibitor, lithium chloride, suppresses NE tumor proliferation and hormone production. Thus, we propose to conduct a Phase II clinical trial to determine if lithium is a potential therapy for patients with NE tumors. The primary objective in this aim is to evaluate the response rate for patients with NE tumors treated with Lithium. The secondary endpoints are: 1) the progression-free and overall survival of patients with NE tumors treated with Lithium; 2) the effect of Lithium on tumor markers specific for NE tumors; 3) the toxicity and tolerability of Lithium in this patient population; 4) the quality of life of patients with NE tumors treated with Lithium and 5) the expression of GSK3B signaling pathway members in the NE tumor samples from patients enrolled in this clinical study before and during lithium therapy. In summary, these studies are part of our long-term goal of designing and developing novel methods to treat and palliate patients with unresectable, metastatic NE tumors. Neuroendocrine (NE) tumors such as carcinoid, islet cell tumors, and medullary thyroid cancer are the second most common cause of isolated hepatic metastases. These tumors often cause debilitating symptoms due to excessive hormonal secretion. Besides surgery, there are limited curative and palliative treatments available to patients with metastatic NE tumors, emphasizing the need for development of other forms of therapy.