H. Lee Moffitt Cancer Center & Research Institute is a nonprofit cancer treatment and research center located in Tampa, Florida Wikipedia.
Zheng X.Q.,H. Lee Moffitt Cancer Center and Research Institute
Oncogene | Year: 2014
Despite the clinical success of tamoxifen, its resistance remains a major challenge in breast cancer. Here we show that Aurora-A determines tamoxifen sensitivity by regulation of oestrogen receptor (ER)α. Ectopic expression of Aurora-A decreases and depletion of Aurora-A enhances tamoxifen sensitivity in ERα-positive breast cancer. Elevated Aurora-A was significantly associated with the recurrence of ERα-positive tumours. Notably, Aurora-A inhibitor MLN8237, which is currently in clinical trial, synergizes with tamoxifen and overcomes tamoxifen resistance. Furthermore, Aurora-A interacts with and phosphorylates ERα on serine-167 and -305, leading to increase in ERα DNA-binding and transcriptional activity. Elevated levels of Aurora-A are significantly associated with disease-free survival in ERα-positive but not ERα-negative breast cancers. These data suggest that Aurora-A has a pivotal role in tamoxifen resistance and ERα is a bona fide substrate of Aurora-A. Thus, Aurora-A represents a prognostic marker in ERα-positive tumour and a critical therapeutic target in tamoxifen-resistant breast cancer, and Aurora-A inhibitor could be used as either an independent or concurrent agent in tamoxifen-resistant tumour.
Turaga K.K.,Medical College of Wisconsin |
Kvols L.K.,H. Lee Moffitt Cancer Center and Research Institute
CA Cancer Journal for Clinicians | Year: 2011
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively rare tumors that arise from the diffuse neuroendocrine system. This heterogeneous group of tumors was often considered a single entity. This belied their biological diversity, and the biggest advance in understanding these tumors over the past decades has been in understanding this diversity. Diagnosis of these tumors has been aided by advances in pathological diagnosis and classification and tumor imaging with endoscopic ultrasound and somatostatin receptor fusion imaging. Genetic and molecular advances have identified molecular targets in the treatment of these tumors. Surgery remains the mainstay of treatment, amply supported by interventional radiological techniques, including embolization. Treatment of metastatic disease has improved significantly with the addition of several new agents, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and yttrium-90-DOTA (1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid) and lutetium-177-DOTA octreotate. Despite significant advances in the understanding and management of GEP-NETs, the survival of patients remains largely unchanged and there remains a need for the development of national and international research collaborations to spearhead future efforts. © 2011 American Cancer Society, Inc.
Tomblyn M.,H. Lee Moffitt Cancer Center and Research Institute
Cancer Control | Year: 2012
Background: Radioimmunotherapy (RIT) is a safe and effective therapeutic option for patients with indolent B-cell non-Hodgkin lymphomas (NHL), in both up-front and relapsed/refractory settings. Two approved agents (90Y-ibritumomab tiuxetan and 131I-tositumomab) are available in the United States. Both target CD20 with similar clinical outcomes but with unique clinical considerations and radiation precautions due to the use of varying radioisotopes. Methods: This paper reviews the available evidence for these approved RIT agents and examines the recently published and ongoing clinical trials of potential novel indications for aggressive B-cell NHL. Results: A pretreatment biodistribution evaluation required before administering the 90Y-ibritumomab tiuxetan therapeutic dose has been removed, which once limited its usage. The potential clinical applications of RIT include relapsed/refractory indolent B-cell NHL, diffuse large B-cell lymphoma, indolent lymphoma in the front-line setting, and mantle cell lymphoma. Multiple novel RIT agents are in preclinical and clinical development, and the addition of radiosensitizers or external-beam radiotherapy may act in synergy with RIT for both indolent and aggressive lymphomas. The risk of treatment-related myelodysplastic syndrome does not appear to be higher in patients treated with RIT over those receiving chemotherapy alone. Conclusions: RIT is a safe, effective, and significantly underutilized therapy for patients with B-cell NHL, and many studies have demonstrated the efficacy of 90Y-ibritumomab tiuxetan and 131I-tositumomab for relapsed/ refractory indolent B-cell lymphomas. Continued research to establish its efficacy for other lymphoma subtypes is warranted.
Creelan B.C.,H. Lee Moffitt Cancer Center and Research Institute
Cancer Control | Year: 2014
Background: The immune checkpoint proteins, including the B7/CD28 receptor superfamily, have become increasingly important targets for pharmacologic blockade. Several classes of new agents have impressive clinical activity, and their eventual approval for treatment of lung cancer seems likely. Methods: This article discusses the current development of these agents, including the CTLA-4, PD-1, and PD-L1 inhibitory pathways, killer immunoglobulin receptor (KIR) inhibition, and other checkpoint proteins. Results: Ipilimumab in combination with chemotherapy has exhibited encouraging results in small-cell and non-small-cell lung cancer alike. Reported phase I trials of the monoclonal antibodies nivolumab, MK-3475, MEDI4736, and MPDL3280A are demonstrating durable overall radiological response rates in the 20% to 25% range in lung cancer. This exceptional activity includes squamous lung cancers, a population historically bereft of significant therapeutic advances. Retrospective examination of tumor PD-L1 expression suggests that PD-L1 may eventually be evaluable as a predictive biomarker. Dual checkpoint blockade strategies, such as those combining anti-CTLA-4, anti-LAG-3, or anti-KIR, are being tested to increase the proportion and durability of tumor responses. Examination of acquired immune resistance and post-immunotherapy relapse strategies are underway. Conclusions: These emerging antibodies hold great potential for the systemic control of epithelial cancers such as lung cancer.
Strosberg J.R.,H. Lee Moffitt Cancer Center and Research Institute
Seminars in Oncology | Year: 2013
Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the "diffuse neuroendocrine system," they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and treatment of these rare neoplasms. © 2013 Elsevier Inc.