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. ? ? ?
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