Phase II Clinical Trial Utilizing Lithium for Patients with Neuroendocrine Tumors

描述（由申请人提供）：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性肝转移的第二大常见原因。由于激素分泌过多，这些肿瘤常常引起衰弱症状。除手术外，转移性NE肿瘤患者的治愈和姑息治疗方法有限，这强调了开发其他形式治疗的必要性。在本提案中，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，我们将证明有效的GSK3B抑制剂氯化锂可以抑制NE肿瘤的增殖和激素的产生。因此，我们建议进行II期临床试验，以确定锂是否是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肿瘤患者的反应率。次要终点是：1)锂治疗的NE肿瘤患者的无进展生存期和总生存期；2)锂对NE肿瘤特异性肿瘤标志物的影响；3)锂在该患者群体中的毒性和耐受性；4)锂治疗的NE肿瘤患者的生活质量；5)锂治疗前和治疗过程中纳入临床研究的NE肿瘤样本中GSK3B信号通路成员的表达。总之，这些研究是我们设计和开发治疗和缓解不可切除的转移性NE肿瘤患者的新方法的长期目标的一部分。神经内分泌（NE）肿瘤，如类癌、胰岛细胞肿瘤和甲状腺髓样癌是孤立性肝转移的第二大常见原因。由于激素分泌过多，这些肿瘤常常引起衰弱症状。除手术外，转移性NE肿瘤患者的治愈和姑息治疗方法有限，这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.