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Neuroendocrine Tumor Research Foundation-AACR Grants

Formerly the Caring for Carcinoid Foundation, the Neuroendocrine Tumor Research Foundation updated its name in 2015 to better reflect the current medical terminology for the disease and to include all those who are affected by neuroendocrine cancer in their community of support. The Neuroendocrine Tumor Research Foundation-AACR Grants represent a joint effort to promote and support innovative cancer research. This grant is available to independent junior and senior investigators to develop and study new ideas and innovative approaches that have direct application and relevance to neuroendocrine tumors. Proposed research may be in any discipline of basic, translational, clinical, or epidemiological cancer research.

2019 Grantee

Azhdarinia_AliAli Azhdarinia, PhD
Assistant Professor
University of Texas Health Science Center at Houston
Houston, Texas
spacerTumor-specific delivery of temozolomide to overcome resistance in GEP-NETs

Scientific Statement of Research
Traditional chemotherapeutics induce systemic toxicities that limit treatment protocols to conservative clinical endpoints instead of seeking long-term tumor regression and cure. Given the goal of maximizing therapeutic index, drug delivery systems have been used to actively target cytotoxics and reduce off-target effects. Image-guided drug delivery is uniquely suited to enhance the therapeutic index of chemotherapy agents based on its intrinsic ability to monitor and quantify drug distribution. To demonstrate the translational feasibility of this approach, the clinical positron emission tomography agent 68Ga-DOTA-TOC will be used as the foundation for developing a peptide-drug conjugate with the DNA alkylating agent temozolomide (TMZ). Receptor-mediated TMZ delivery could overcome the effects of neuroendocrine tumor heterogeneity, potentially making it a universal, tumor-specific chemotherapy agent for somatostatin receptor subtype 2-positive tumors. Targeted TMZ delivery may also produce sufficiently high tumor doses capable of overcoming resistance mechanisms in a manner that is not possible with systemic administration.

Biography
Dr. Azhdarinia is an associate professor of molecular medicine in the Brown Foundation Institute of Molecular Medicine at the University of Texas Health Science Center at Houston. Dr. Azhdarinia received his bachelor’s degree in biology from the University of Houston, followed by completion of his master’s degree and PhD in pharmacology from the University of Texas Graduate School of Biomedical Sciences in Houston. His research training was in the area of contrast agent development with a focus on radiopharmaceutical development. Dr. Azhdarinia’s research interests are in utilizing molecular targeting strategies for the detection and treatment of cancer.

Acknowledgement of Support
The 2019 Neuroendocrine Tumor Research Foundation-AACR Grant will allow my laboratory to develop a drug delivery approach that uniquely combines clinically proven imaging and therapy moieties into a single agent. The funding critically supports my long-term goal of introducing new precision therapies for patients with neuroendocrine tumors.

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2018 Grantee

Pawel Mazur, PhDPawel Mazur, PhD
Assistant Professor
University of Texas MD Anderson Cancer Center
Houston, Texas
Spacer_1 lineNext generation animal models to define therapies for neuroendocrine tumors

Scientific Statement of Research
Our overarching goal is to better understand the role of lysine methylation of cellular proteins in neuroendocrine tumor development. To explore possible connections between over 100 methyltransferases and tumorigenesis we performed a high-content genetic screen. We identified NSD3 enzyme as a key driver of neuroendocrine tumor progression and drug resistance. However, the catalytic activity and substrate specificity of NSD3 in neuroendocrine tumors remains unknown. We hypothesize that NSD3 enzymatic activity cooperates with oncogenic signaling to promote the unlimited expansion of neuroendocrine cells. We will use a multi-disciplinary strategy to characterize NSD3 methylation activity and elucidate the molecular mechanisms and pathways by which NSD3 promotes tumorigenesis. To validate the function and therapeutic potential of NSD3 we have generated a pre-clinical mouse model of pancreatic neuroendocrine tumors faithfully recapitulating human disease. The major, long-term impact of our studies will be the development of novel therapeutic strategies to treat several types of devastating neuroendocrine cancers.

Biography
Dr. Mazur earned his PhD degree in 2011 in the Max Planck Institute of Biochemistry and University of Munich, Germany. From 2011 to 2016 Dr. Mazur completed his postdoctoral fellowship at Stanford University, in the laboratory of Dr. Julien Sage. Since 2017, Dr. Mazur is an assistant professor at MD Anderson Cancer Center. Dr. Mazur’s research uncovered the function of several orphan enzymes that provided new links between protein modification and cancer biology. His lab aims to harness protein post translation modification signaling to cancer therapy. Dr. Mazur's work is supported by the NIH Pathway to Independence, CPRIT Rising Star Award and Sanofi Innovation Award.

Acknowledgement of Support
Unique mechanisms that drive neuroendocrine tumors development are not fully recognized. Our progress is hindered by the lack of proper pre-clinical models of the disease. The award provides critically needed resources to build a comprehensive cancer modeling platform to identify and validate novel therapeutics using accurate animal models that faithfully recapitulate human disease.

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2017 Grantee

Gorski_90x110.jpgSharon Gorski, PhD
Senior Scientist
Genome Sciences Center
Vancouver, BC, Canada
Proteogenomic analysis of pancreatic neuroendocrine tumors

Scientific Statement of Research
Pancreatic neuroendocrine tumors (PNETs) are an under-studied type of neuroendocrine tumor that are rare but clinically challenging due to late detection, variable progression, and frequent metastasis. The molecular basis of PNETs is not well understood and there are no prognostic markers to aid PNET clinical management. The overall aim of this study is to provide a comprehensive molecular characterization of PNETs to better understand disease progression and to devise clinically relevant subclasses. Dr. Gorski’s team has available both discovery and validation cohorts, including metastatic PNET cases. By integrating RNA-sequencing based transcriptome profiling and an innovative new technology for proteomic profiling of tumor specimens, their study will be the first to explore the proteogenomic landscape of PNETs. In addition to identifying disease classifiers, this study will lay the groundwork for further investigations of candidate biomarkers, potential driver mutations, and therapeutic targets.

Biography
Dr. Gorski completed a PhD in biology and biomedical bciences at Washington University School of Medicine, St. Louis, Missouri, in 1999. She then conducted postdoctoral studies at the British Columbia Cancer Agency where she utilized genomics approaches to study cell death and cell survival pathways. Dr. Gorski is currently a senior scientist at the BC Cancer Agency’s Genome Sciences Centre and a professor in the Department of Molecular Biology and Biochemistry at Simon Fraser University. Her research program includes analysis of cancer-related signaling pathways with a focus on breast and pancreatic cancers.

Acknowledgement of Support
We are very grateful for the 2017 Neuroendocrine Tumor Research Foundation-AACR Grant that will enable us to generate the first proteogenomics resource for pancreatic neuroendocrine tumors. This unique resource has the potential to improve the clinical management of this disease, increase our knowledge of disease progression, and identify new therapeutic avenues for patients.

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