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Pancreatic Neoplasms: HELP
Articles by Dr. Anirban Maitra
Based on 196 articles published since 2008
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Between 2008 and 2019, Anirban Maitra wrote the following 196 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Guideline Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. 2017

Khorana, Alok A / Mangu, Pamela B / Berlin, Jordan / Engebretson, Anitra / Hong, Theodore S / Maitra, Anirban / Mohile, Supriya G / Mumber, Matthew / Schulick, Richard / Shapiro, Marc / Urba, Susan / Zeh, Herbert J / Katz, Matthew H G. ·Alok A. Khorana and Marc Shapiro, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Jordan Berlin, Vanderbilt University, Nashville, TN · Anitra Engebretson, Pancreatic Cancer Action Network, Manhattan Beach, CA · Theodore S. Hong, Massachusetts General Hospital, Boston, MA · Anirban Maitra and Matthew H.G. Katz, The University of Texas MD Anderson Cancer Center, Houston, TX · Supriya G. Mohile, University of Rochester, Rochester, NY · Matthew Mumber, Harbin Clinic, Rome, GA · Richard Schulick, University of Colorado at Denver, Denver, CO · Susan Urba, University of Michigan, Ann Arbor, MI · and Herbert J. Zeh, University of Pittsburgh, Pittsburgh, PA. ·J Clin Oncol · Pubmed #28398845.

ABSTRACT: Purpose To update the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline published on May 31, 2016. The October 2016 update focuses solely on new evidence that pertains to clinical question 4 of the guideline: What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor? Methods The recently published results of a randomized phase III study prompted an update of this guideline. The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations. Results The ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma. Median overall survival was improved in the doublet arm to 28.0 months (95% CI, 23.5 to 31.5 months) versus 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm. Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery. The remaining recommendations from the original 2016 ASCO guideline are unchanged.

2 Editorial Intercepting Pancreatic Cancer: Our Dream Team's Resolve to Stop Pancreatic Cancer. 2018

Goggins, Michael G / Lippman, Scott M / Constantinou, Pamela E / Jacks, Tyler / Petersen, Gloria M / Syngal, Sapna / Maitra, Anirban. ·Division of Hematology/Oncology, Department of Medicine, Moores Center for Personalized Cancer Therapy, University of California, San Diego, La Jolla, CA. · Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. ·Pancreas · Pubmed #30325853.

ABSTRACT: -- No abstract --

3 Editorial A New Scalpel for the Treatment of Pancreatic Cancer: Targeting Stromal-Derived STAT3 Signaling. 2015

Cowan, Robert W / Maitra, Anirban / Rhim, Andrew D. ·Division of Gastroenterology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan. · Departments of Pathology and Translational Molecular Pathology, Sheikh Ahmed Pancreatic Cancer Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas. · Division of Gastroenterology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan. Electronic address: arhim@med.umich.edu. ·Gastroenterology · Pubmed #26526714.

ABSTRACT: -- No abstract --

4 Editorial New insights into plasticity of pancreatic cancer: cancer to acinar cell reprogramming by the basic helix-loop-helix transcription factor E47. 2015

Bailey, Jennifer M / Hendley, Audrey M / Maitra, Anirban. ·From the *Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston; and †Departments of Pathology and Molecular Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. ·Pancreas · Pubmed #26061556.

ABSTRACT: -- No abstract --

5 Editorial Tracking down the hedgehog's lair in the pancreas. 2010

Maitra, Anirban. · ·Gastroenterology · Pubmed #20100446.

ABSTRACT: -- No abstract --

6 Review Early Detection of Pancreatic Cancer: Opportunities and Challenges. 2019

Singhi, Aatur D / Koay, Eugene J / Chari, Suresh T / Maitra, Anirban. ·Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas; Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: Chari.suresh@mayo.edu. · Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas. ·Gastroenterology · Pubmed #30721664.

ABSTRACT: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with symptomatic, surgically unresectable disease. Although the goal of early detection of PDAC is laudable and likely to result in significant improvement in overall survival, the relatively low prevalence of PDAC renders general population screening infeasible. The challenges of early detection include identification of at-risk individuals in the general population who would benefit from longitudinal surveillance programs and appropriate biomarker and imaging-based modalities used for PDAC surveillance in such cohorts. In recent years, various subgroups at higher-than-average risk for PDAC have been identified, including those with familial risk due to germline mutations, a history of pancreatitis, patients with mucinous pancreatic cysts, and elderly patients with new-onset diabetes. The last 2 categories are discussed at length in terms of the opportunities and challenges they present for PDAC early detection. We also discuss current and emerging imaging modalities that are critical to identifying early, potentially curable PDAC in high-risk cohorts on surveillance.

7 Review Intraductal Papillary Mucinous Neoplasms of the Pancreas: Current Understanding and Future Directions for Stratification of Malignancy Risk. 2018

Fonseca, Annabelle L / Kirkwood, Kimberly / Kim, Michael P / Maitra, Anirban / Koay, Eugene J. · ·Pancreas · Pubmed #29424809.

ABSTRACT: The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.

8 Review Recent advances in genomic profiling of adenosquamous carcinoma of the pancreas. 2017

Marcus, Rebecca / Maitra, Anirban / Roszik, Jason. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Departments of Pathology and Translational Molecular Pathology, Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ·J Pathol · Pubmed #28816351.

ABSTRACT: Adenosquamous carcinoma of the pancreas (ASCP) is a mixed tumor type which contains squamous cell carcinoma and also ductal adenocarcinoma components. Due to the rarity of this malignancy, only very limited genomic profiling has been performed. A recent paper by Fang et al. published in The Journal of Pathology contributed to our knowledge of genomic alterations by performing whole-genome and -exome sequencing of 17 ASCP tumors. They found major genomic similarities to pancreatic ductal adenocarcinoma; however, the p53 pathway was altered in a greater proportion of cases, while a high frequency of 3p loss was a distinct copy number alteration pattern observed in ASCP. Laser capture microdissection revealed that adenocarcinoma and squamous carcinoma components of ASCP harbor similar genomic variations, indicating that the origin of tumor components is the same or similar. Although the study published by Fang et al. increases our knowledge of this rare mixed tumor type, further investigation, including RNA sequencing, will be needed to fully characterize this malignancy and to aid the development of novel treatment approaches. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

9 Review The role of stromal cancer-associated fibroblasts in pancreatic cancer. 2017

von Ahrens, Dagny / Bhagat, Tushar D / Nagrath, Deepak / Maitra, Anirban / Verma, Amit. ·Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA. · Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA. · The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. · Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA. averma@aecom.yu.edu. ·J Hematol Oncol · Pubmed #28351381.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6. The role of downstream signaling pathways including JAK/STAT, mTOR, sonic hedge hog (SHH), and NFkB have also been shown to play an important function in PDAC-CAF cross talk. The role of autophagy and other metabolic effects on each cell type within the tumor have also been proposed to play roles in facilitating CAF secretory function and enhancing tumor growth in a low-glucose microenvironment. Targeting the stroma has gained interest with multiple preclinical and clinical trials targeting SHH, JAK2, and methods of either exploiting the secretory capability of CAFs to enhance drug delivery or inhibiting it to prevent its influence on cancer cell chemoresistance. This review summarizes the most recent progress made in understanding stromal formation; its contribution to tumor proliferation, invasion, and metastasis; its role in chemoresistance; and potential therapeutic strategies on the horizon.

10 Review Preclinical Rationale for the Phase III Trials in Metastatic Pancreatic Cancer: Is Wishful Thinking Clouding Successful Drug Development for Pancreatic Cancer? 2017

Thota, Ramya / Maitra, Anirban / Berlin, Jordan D. ·From the *Division of Hematology/Oncology, Vanderbilt University, Nashville, TN; and †Sheikh Ahmed Pancreatic Cancer Research Center, Departments of Pathology and Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX. ·Pancreas · Pubmed #28085753.

ABSTRACT: Prior phase III trials in advanced pancreatic cancer have been predominantly unsuccessful. In this review, we attempt to understand how past preclinical data were translated into phase III clinical trials in metastatic pancreatic cancer as described in the article. A systematic literature review conducted through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, from January 1997 to June 2015 using key words-phase III clinical trials, metastatic/advanced pancreatic adenocarcinoma or pancreatic cancer identified 30 randomized controlled trials (RCTs) that met criteria. The trials were limited to RCTs in the first-line treatment of patients with metastatic pancreatic cancer. The success rate of first-line phase III studies in advanced pancreatic cancer was only 13%. In 60% of the RCTs, no preclinical experiments were referenced in biologically cognate pancreatic models. Nine (30%) of the RCTs were designed based on preclinical evidence from in vitro cell lines alone without additional in vivo validation in xenograft models. It remains uncertain how strongly the preclinical data influence the development of clinical regimens but so far the studies developed based on more solid preclinical evidence have been successful.

11 Review Molecular and Genetic Basis of Pancreatic Carcinogenesis: Which Concepts May be Clinically Relevant? 2016

Bernard, Vincent / Fleming, Jason / Maitra, Anirban. ·Sheikh Ahmed Pancreatic Cancer Research Center, UT MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. · Sheikh Ahmed Pancreatic Cancer Research Center, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. · Sheikh Ahmed Pancreatic Cancer Research Center, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Room Z3.3038, Houston, TX 77030, USA. Electronic address: amaitra@mdanderson.org. ·Surg Oncol Clin N Am · Pubmed #27013361.

ABSTRACT: Carcinogenic progression in the pancreas arises through a well-established stepwise accumulation of molecular aberrations from a normal cell to an invasive adenocarcinoma. Recent large-scale sequencing efforts have provided insight into novel driver genes as well as enriched core signaling pathways that underlie the inherent heterogeneity found in pancreatic cancer. By exploiting these genomic profiles, we may begin to provide new insights into patient stratification and therapeutic guidance. This review discusses the molecular landscape of pancreatic cancer and its role in tumor progression, clinical prognostication, and the development of novel therapeutic strategies.

12 Review Changing the course of pancreatic cancer--Focus on recent translational advances. 2016

Javle, Milind / Golan, Talia / Maitra, Anirban. ·MD Anderson Cancer Center, 1515, Holcombe Blvd, Unit 426, Houston, TX 77030, USA. · Sheba Medical Center, Tel Hashomer 52621, Israel. ·Cancer Treat Rev · Pubmed #26924195.

ABSTRACT: In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are "KRAS equal"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents. Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.

13 Review Genetics and biology of pancreatic ductal adenocarcinoma. 2016

Ying, Haoqiang / Dey, Prasenjit / Yao, Wantong / Kimmelman, Alec C / Draetta, Giulio F / Maitra, Anirban / DePinho, Ronald A. ·Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; · Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; · Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; · Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; · Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; · Department of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Sheikh Ahmed Pancreatic Cancer Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ·Genes Dev · Pubmed #26883357.

ABSTRACT: With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses. A deeper understanding of cancer cell biology, particularly altered cancer cell metabolism and impaired DNA repair processes, is providing novel therapeutic strategies that show strong preclinical activity. Elucidation of tumor biology principles, most notably a deeper understanding of the complexity of immune regulation in the tumor microenvironment, has provided an exciting framework to reawaken the immune system to attack PDAC cancer cells. While the long road of translation lies ahead, the path to meaningful clinical progress has never been clearer to improve PDAC patient survival.

14 Review The emerging roles of F-box proteins in pancreatic tumorigenesis. 2016

Wang, Hua / Maitra, Anirban / Wang, Huamin. ·Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, United States. · Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, United States; Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, United States. · Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, United States; Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, United States. Electronic address: hmwang@mdanderson.org. ·Semin Cancer Biol · Pubmed #26384530.

ABSTRACT: The role of F-box proteins in pancreatic tumorigenesis is emerging owing to their pivotal and indispensable roles in cell differentiation, cell cycle regulation and proliferation. In this review, we will focus on β-TrCP (β-transducin repeat-containing protein) and two other prototypical mammalian F-box proteins, Fbxw7 and Fbxw8, in pancreatic tumorigenesis and progression. We will highlight the functions and regulation of these F-box proteins, their respective substrates and cross-talks with other key signaling pathways, such as the Ras-Raf-Mek-Erk, Hedgehog, NFκB, TGF-β, Myc and HPK1 signaling pathways in pancreatic cancer.

15 Review Early detection of sporadic pancreatic cancer: summative review. 2015

Chari, Suresh T / Kelly, Kimberly / Hollingsworth, Michael A / Thayer, Sarah P / Ahlquist, David A / Andersen, Dana K / Batra, Surinder K / Brentnall, Teresa A / Canto, Marcia / Cleeter, Deborah F / Firpo, Matthew A / Gambhir, Sanjiv Sam / Go, Vay Liang W / Hines, O Joe / Kenner, Barbara J / Klimstra, David S / Lerch, Markus M / Levy, Michael J / Maitra, Anirban / Mulvihill, Sean J / Petersen, Gloria M / Rhim, Andrew D / Simeone, Diane M / Srivastava, Sudhir / Tanaka, Masao / Vinik, Aaron I / Wong, David. ·From the *Department of Medicine, Mayo Clinic, Rochester, MN; †Department of Biomedical Engineering, University of Virginia, Charlottesville, VA; Departments of ‡Biochemistry and Molecular Biology, §Pathology and Microbiology, and ∥Surgery, Fred & Pamela Buffett Cancer Center, University of Nebraska, Omaha, NE; ¶Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD; #Division of Gastroenterology, University of Washington, Seattle, WA; **Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD; ††Sawgrass Leadership Institute, Ponte Vedra Beach, FL; ‡‡Department of Surgery, University of Utah, Salt Lake City, UT; §§Department of Radiology, Stanford University School of Medicine, Stanford; ∥∥Department of Medicine, David Geffen School of Medicine, and ¶¶General Surgery, University of California Los Angeles, Los Angeles, CA; ##Kenner Family Research Fund; ***Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; †††Department of Internal Medicine, University of Greifswald, Greifswald, Germany; ‡‡‡Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX; §§§Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥∥∥Gastroenterology Division, Department of Internal Medicine and Comprehensive Cancer Center, and ¶¶¶Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, MI; ###Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD; ****Departments of Surgery and Oncology, Kyushu University, Fukuoka, Japan; ††††Department of Medicine, Eastern Virginia Medical School, Norfolk, VA; and ‡‡‡‡Division of Oral Biology and Medicine, CLA School of Dentistry, Jonnson Comprehensive Cancer Center, University of California Los Angeles, L ·Pancreas · Pubmed #25931254.

ABSTRACT: Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

16 Review Genetic progression of pancreatic cancer. 2014

Cowan, Robert W / Maitra, Anirban. ·From the Department of Pathology and Translational Molecular Pathology, Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX. ·Cancer J · Pubmed #24445769.

ABSTRACT: The progression from normal cells to invasive pancreatic ductal adenocarcinoma (PDAC) requires the accumulation of multiple inherited or acquired mutations. Activating point mutations in the KRAS oncogene are prevalent in pancreatic cancer and result in the stimulation of several pathways including the RAF-mitogen-activated protein kinase pathway and the phosphoinositide 3-kinase pathway. Other genetic alterations, including telomere shortening and the inactivation of tumor suppressor genes such as CDKN2A, TP53, and SMAD4, which encode p16, p53, and SMAD4, respectively, also contribute to the progression of pancreatic cancer. These, and other genetic events, can present at different stages in the development of PDAC at histologically defined precursor lesions known as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, or mucinous cystic neoplasms. Each precursor lesion represents alternate routes to PDAC formation and has a unique presentation and somewhat distinct genetic events controlling its development. Despite the advances in the understanding of the genetics of PDAC, the prognosis for this cancer remains poor, and several important aspects of its pathogenesis must be clarified to improve therapeutics, including the timing and method of metastases, as well as the relationship of the tumor cells with the desmoplastic stroma, which is a characteristic feature of the cancer. This review discusses the principal genetic alterations in PDAC and its precursor lesions, including their effects on promoting carcinogenesis.

17 Review Identification and analysis of precursors to invasive pancreatic cancer. 2013

Matthaei, Hanno / Dal Molin, Marco / Maitra, Anirban. ·Department of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ·Methods Mol Biol · Pubmed #23359146.

ABSTRACT: Precursor lesions of pancreatic cancer have been recognized about a century ago. The development of a consistent reproducible nomenclature and classification system for these lesions has been a major advance in the study of these noninvasive precursors. Pancreatic intraepithelial neoplasia (PanIN) as microscopic precursor lesions can be distinguished from mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMN) that are cystic and can often be recognized on imaging. Since precursor lesions harbor the unique chance to treat a patient before a fatal pancreatic cancer can arise a molecular characterization is essential to understand the biology and to find diagnostic and therapeutic targets to fight this disease of near uniform lethality. In order to study precursor lesions on a molecular level a meticulous isolation of the neoplastic cells is inevitable. We present the salient histopathologic and molecular features of precursor lesions of pancreatic cancer as well as methods that have proved to be useful within experimental studies.

18 Review Human correlates of provocative questions in pancreatic pathology. 2012

McDonald, Oliver G / Maitra, Anirban / Hruban, Ralph H. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·Adv Anat Pathol · Pubmed #23060061.

ABSTRACT: Studies of cell lines and of animal models of pancreatic cancer have raised a number of provocative questions about the nature and origins of human pancreatic cancer and have provided several leads into exciting new approaches for the treatment of this deadly cancer. In addition, clinicians with little or no contact with human pathology have challenged the way that pancreatic pathology is practiced, suggesting that "genetic signals" may be more accurate than today's multimodal approach to diagnoses. In this review, we consider 8 provocative issues in pancreas pathology, with an emphasis on "the evidence derived from man."

19 Review Conceptual framework for cutting the pancreatic cancer fuel supply. 2012

Le, Anne / Rajeshkumar, N V / Maitra, Anirban / Dang, Chi V. ·Departments of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·Clin Cancer Res · Pubmed #22896695.

ABSTRACT: Pancreatic ductal adenocarcinoma (a.k.a. pancreatic cancer) remains one of the most feared and clinically challenging diseases to treat despite continual improvements in therapies. The genetic landscape of pancreatic cancer shows near ubiquitous activating mutations of KRAS, and recurrent inactivating mutations of CDKN2A, SMAD4, and TP53. To date, attempts to develop agents to target KRAS to specifically kill cancer cells have been disappointing. In this regard, an understanding of cellular metabolic derangements in pancreatic cancer could lead to novel therapeutic approaches. Like other cancers, pancreatic cancer cells rely on fuel sources for homeostasis and proliferation; as such, interrupting the use of two major nutrients, glucose and glutamine, may provide new therapeutic avenues. In addition, KRAS-mutant pancreatic cancers have been documented to depend on autophagy, and the inhibition of autophagy in the preclinical setting has shown promise. Herein, the conceptual framework for blocking the pancreatic fuel supply is reviewed.

20 Review Heterogeneity and targeting of pancreatic cancer stem cells. 2012

Penchev, Vesselin R / Rasheed, Zeshaan A / Maitra, Anirban / Matsui, William. ·Department of Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·Clin Cancer Res · Pubmed #22896694.

ABSTRACT: Cancer stem cells (CSC) have been identified in an ever-increasing number of human malignancies on the basis of their ability to recapitulate tumors in the ectopic setting and maintain long-term tumorigenic potential. In addition, in pancreatic adenocarcinoma, CSCs may display additional properties, such as relative drug resistance and enhanced invasive and migratory potential that implicate a role in disease pathogenesis spanning initial tumor formation to metastatic disease progression. Importantly, these findings also indicate that the development of novel therapeutic strategies capable of inhibiting or eliminating CSCs will improve clinical outcomes. Preclinical studies have already described a wide array of potential approaches that target CSC-specific surface antigens and cellular pathways involved in cell survival, adhesion, self-renewal, and differentiation. Further, progress in this area should continue to move forward as the unique biology of CSCs is better understood. All preclinical studies to date have focused on targeting specific and phenotypically defined CSCs, but multiple cell populations with the ability to form tumors and self-renew have been identified in pancreatic carcinoma. As the clinical efficacy of CSC-directed therapies will depend on the inhibition of all sources of tumor self-renewal, better understanding of how specific CSC populations are related to one another and whether each possesses specific functional properties will be critical. In this CCR Focus article, we discuss the potential relationships between different pancreatic CSC populations and strategies to identify novel targeting approaches.

21 Review Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy. 2012

de Wilde, Roeland F / Edil, Barish H / Hruban, Ralph H / Maitra, Anirban. ·The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, 1550 Orleans Street Baltimore, MD 21231, USA. ·Nat Rev Gastroenterol Hepatol · Pubmed #22310917.

ABSTRACT: Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise ∼1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of ∼65% and a 10-year survival of 45% for resected lesions. As PanNETs have a low incidence, they have been understudied, with few advances made until the completion of their exomic sequencing in the past year. In this Review, we summarize some of the latest insights into the genetics of PanNETs, and their probable implications in the context of prognosis and therapy. In particular, we discuss two genes (DAXX and ATRX) that have collectively been identified as mutated in >40% of PanNETs, and the biological and prognostic implications of these novel mutations. The identification of recurrent somatic mutations within the mTOR signaling pathway and the therapeutic implications for personalized therapy in patients with PanNETs are also discussed. Finally, this Review outlines state-of-the-art advances in the biology of PanNETs that are of emerging translational importance.

22 Review Cystic precursors to invasive pancreatic cancer. 2011

Matthaei, Hanno / Schulick, Richard D / Hruban, Ralph H / Maitra, Anirban. ·The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD 21231, USA. ·Nat Rev Gastroenterol Hepatol · Pubmed #21383670.

ABSTRACT: Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not.

23 Review Agents targeting the Hedgehog pathway for pancreatic cancer treatment. 2010

Bisht, Savita / Brossart, Peter / Maitra, Anirban / Feldmann, Georg. ·Department of Internal Medicine 3, Center of Integrated Oncology Cologne-Bonn, University of Bonn, Wilhelmstrasse 35-37, Bonn, Germany. ·Curr Opin Investig Drugs · Pubmed #21154121.

ABSTRACT: Recent evidence has demonstrated that aberrant reactivation of the Hedgehog signaling pathway contributes to tumor initiation and progression in various human malignancies, including pancreatic cancer; therefore, the Hedgehog pathway has emerged as a promising novel therapeutic target. Initial translational studies conducted using cyclopamine, a small-molecule inhibitor of the Smoothened (SMO) component of the Hedgehog pathway, demonstrated that pharmacological blockade of aberrant Hedgehog signaling has the potential to inhibit tumor initiation, progression and metastatic spread. This concept has been corroborated using different compounds in various preclinical models of pancreatic cancer and other malignancies; several of these studies suggest possible therapeutic synergisms of Hedgehog inhibitors with established antineoplastic agents. This review provides a concise overview of translational studies assessing the use of Hedgehog inhibitors as novel therapeutic strategy for cancer, particularly pancreatic cancer.

24 Review Pancreatic intraepithelial neoplasia and pancreatic tumorigenesis: of mice and men. 2009

Ottenhof, Niki A / Milne, Anya N A / Morsink, Folkert H M / Drillenburg, Paul / Ten Kate, Fiebo J W / Maitra, Anirban / Offerhaus, G Johan. ·Department of Pathology, University Medical Center, Utrecht, the Netherlands. ·Arch Pathol Lab Med · Pubmed #19260743.

ABSTRACT: CONTEXT: Pancreatic cancer has a poor prognosis with a 5-year survival of less than 5%. Early detection is at present the only way to improve this outlook. This review focuses on the recent advances in our understanding of pancreatic carcinogenesis, the scientific evidence for a multistaged tumor progression, and the role genetically engineered mouse models can play in recapitulating the natural course and biology of human disease. OBJECTIVES: To illustrate the stepwise tumor progression of pancreatic cancer and genetic alterations within the different stages of progression and to review the findings made with genetically engineered mouse models concerning pancreatic carcinogenesis. DATA SOURCES: A review of recent literature on pancreatic tumorigenesis and genetically engineered mouse models. CONCLUSIONS: Pancreatic cancer develops through stepwise tumor progression in which preinvasive stages, called pancreatic intraepithelial neoplasia, precede invasive pancreatic cancer. Genetic alterations in oncogenes and tumor suppressor genes underlying pancreatic cancer are also found in pancreatic intraepithelial neoplasia. These mutations accumulate during progression through the consecutive stages of pancreatic intraepithelial neoplasia lesions. Also in genetically engineered mouse models of pancreatic ductal adenocarcinoma, tumorigenesis occurs through stepwise progression via consecutive mouse pancreatic intraepithelial neoplasia, and these models provide important tools for clinical applications. Nevertheless differences between mice and men still remain.

25 Review Pancreatic carcinogenesis. 2008

Koorstra, Jan-Bart M / Hustinx, Steven R / Offerhaus, G Johan A / Maitra, Anirban. ·Department of Pathology, University Medical Center, Utrecht, The Netherlands. ·Pancreatology · Pubmed #18382097.

ABSTRACT: Pancreatic cancer is an almost universally lethal disease. Research over the last two decades has shown that pancreatic cancer is fundamentally a genetic disease, caused by inherited germline and acquired somatic mutations in cancer-associated genes. Multiple alterations in genes that are important in pancreatic cancer progression have been identified, including tumor suppressor genes, oncogenes, and genome maintenance genes. Furthermore, the identification of noninvasive precursor lesions of pancreatic adenocarcinoma has led to the formulation of a multi-step progression model of pancreatic cancer and the subsequent identification of early and late genetic alterations culminating in invasive cancer. In addition, an increased understanding of the molecular basis of the disease has facilitated the identification of new drug targets enabling rational drug design. The elucidation of genetic alterations in combination with the development of high-throughput sensitive techniques should lead to the discovery of effective biomarkers for early detection of this malignancy. This review focuses mainly on the current knowledge about the molecular insights of the pathogenesis of pancreatic ductal adenocarcinoma.

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