Pancreatic Cancer Action Network-AACR Innovative Grants
Pancreatic Cancer Action Network-AACR Innovative Grants are available to independent junior and senior investigators to develop and study new ideas and approaches that have direct application and relevance to pancreatic cancer. The research proposed for funding may be basic, translational, clinical, or epidemiological in nature. The Pancreatic Cancer Action Network-AACR Innovative Grants were formally known as the Pancreatic Cancer Action Network-AACR Pilot Grants and have been renamed to emphasize the focus on funding new, creative, and cutting-edge ideas and approaches.
Pancreatic Cancer Action Network-AACR Innovative Grant, in memory of Robert Aronson
Anirban Maitra, MBBS
Co-director and Scientific Director
Sheikh Ahmed Bin Zayed Al Nahyan Center
University of Texas MD Anderson Cancer Center
Macrophage Function in Pancreatic Cancer-associated Diabetes
Pancreatic ductal adenocarcinoma (“pancreatic cancer”) is a strongly diabetogenic entity, with half to two-thirds of patients harboring a new diagnosis of diabetes mellitus (DM) within the prior 36 months. By the time cancer-specific symptoms manifest in these patients, the neoplasm is often advanced, underscoring a missed opportunity for early diagnosis. Unfortunately, while over a million Americans are diagnosed with new Type 2 DM each year, those with an occult pancreatic cancer are significantly less (<1%). Clearly, “reflex” screening of every elderly new-onset type 2 DM for underlying pancreatic cancer is neither practical nor economical. There is an unmet need for an intermediate biomarker that can differentiate patients who merit further screening, from those who do not. Marcophages are known to play an unequivocal role in the pathogenesis of Type 2 DM. Two specific aims are proposed: first, to obtain a snapshot of inflammation, macrophage activity, and biomarkers of insulin resistance in pancreatic cancer patients with and without DM, newly diagnosed Type 2 DM patients without overt malignancy, and other cancer controls (N=30 per cohort, 120 patients overall). Second, to determine in a prospective study of surgically resected patients with pancreatic cancer-associated DM (N=30), the natural history of macrophage phenotype over a 12 month period, including in the pre- and postoperative stages of disease. Specifically, biomarkers of inflammation (high sensitivity C-reactive protein [HsCRP], Leptin, Adiponectin), oxidative stress (oxidized LDL, Nitrotyrosine), monocyte biology (ratios of M1/M2 phenotype, toll-like receptors TLR2/TLR4, and Th1/2 cytokines), and insulin sensitivity, including blood glucose, insulin, and HOMA-IR (a homeostatic model for calculating insulin resistance) will be assessed. As a prelude to translation, the compendium of studies proposed here are geared towards a Point-Care-Testing (POCT) setting, and are currently performed in as little as 1mL of whole blood obtained during a routine draw. This proposal is innovative because it addresses functional distinctions in the pathophysiology of hyperglycemia between Type 2 DM and pancreatic cancer-associated DM, one or more of which can be utilized as a potential intermediate biomarker for early diagnosis in an at-risk population.
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