Literature DB >> 26385075

Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine.

Erik S Knudsen1, Eileen M O'Reilly2, Jonathan R Brody3, Agnieszka K Witkiewicz4.   

Abstract

Patients with pancreatic ductal adenocarcinoma (PDA) have a poor prognosis despite new treatments; approximately 7% survive for 5 years. Although there have been advances in systemic, primarily cytotoxic, therapies, it has been a challenge to treat patients with PDA using targeted therapies. Sequence analyses have provided a wealth of information about the genetic features of PDA and have identified potential therapeutic targets. Preclinical and early-phase clinical studies have found specific pathways could be rationally targeted; it might also be possible to take advantage of the genetic diversity of PDAs to develop therapeutic agents. The genetic diversity and instability of PDA cells have long been thought of as obstacles to treatment, but are now considered exploitable features. We review the latest findings in pancreatic cancer genetics and the promise of targeted approaches in PDA therapy.
Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Kras; Myc; Notch; Smad4

Mesh:

Year:  2015        PMID: 26385075      PMCID: PMC5010785          DOI: 10.1053/j.gastro.2015.08.056

Source DB:  PubMed          Journal:  Gastroenterology        ISSN: 0016-5085            Impact factor:   22.682


  134 in total

1.  Detection of high incidence of K-ras oncogenes during human colon tumorigenesis.

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Journal:  Nature       Date:  1987 May 28-Jun 3       Impact factor: 49.962

2.  CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers.

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Journal:  Cancer Res       Date:  2014-07-01       Impact factor: 12.701

Review 3.  The history and future of targeting cyclin-dependent kinases in cancer therapy.

Authors:  Uzma Asghar; Agnieszka K Witkiewicz; Nicholas C Turner; Erik S Knudsen
Journal:  Nat Rev Drug Discov       Date:  2015-02       Impact factor: 84.694

Review 4.  SWI/SNF nucleosome remodellers and cancer.

Authors:  Boris G Wilson; Charles W M Roberts
Journal:  Nat Rev Cancer       Date:  2011-06-09       Impact factor: 60.716

5.  Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas.

Authors:  M Schutte; R H Hruban; J Geradts; R Maynard; W Hilgers; S K Rabindran; C A Moskaluk; S A Hahn; I Schwarte-Waldhoff; W Schmiegel; S B Baylin; S E Kern; J G Herman
Journal:  Cancer Res       Date:  1997-08-01       Impact factor: 12.701

6.  Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development.

Authors:  Jian Wu; Hanno Matthaei; Anirban Maitra; Marco Dal Molin; Laura D Wood; James R Eshleman; Michael Goggins; Marcia I Canto; Richard D Schulick; Barish H Edil; Christopher L Wolfgang; Alison P Klein; Luis A Diaz; Peter J Allen; C Max Schmidt; Kenneth W Kinzler; Nickolas Papadopoulos; Ralph H Hruban; Bert Vogelstein
Journal:  Sci Transl Med       Date:  2011-07-20       Impact factor: 17.956

7.  Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma.

Authors:  Andrew J Aguirre; Nabeel Bardeesy; Manisha Sinha; Lyle Lopez; David A Tuveson; James Horner; Mark S Redston; Ronald A DePinho
Journal:  Genes Dev       Date:  2003-12-17       Impact factor: 11.361

8.  Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.

Authors:  Marcin Imielinski; Alice H Berger; Peter S Hammerman; Bryan Hernandez; Trevor J Pugh; Eran Hodis; Jeonghee Cho; James Suh; Marzia Capelletti; Andrey Sivachenko; Carrie Sougnez; Daniel Auclair; Michael S Lawrence; Petar Stojanov; Kristian Cibulskis; Kyusam Choi; Luc de Waal; Tanaz Sharifnia; Angela Brooks; Heidi Greulich; Shantanu Banerji; Thomas Zander; Danila Seidel; Frauke Leenders; Sascha Ansén; Corinna Ludwig; Walburga Engel-Riedel; Erich Stoelben; Jürgen Wolf; Chandra Goparju; Kristin Thompson; Wendy Winckler; David Kwiatkowski; Bruce E Johnson; Pasi A Jänne; Vincent A Miller; William Pao; William D Travis; Harvey I Pass; Stacey B Gabriel; Eric S Lander; Roman K Thomas; Levi A Garraway; Gad Getz; Matthew Meyerson
Journal:  Cell       Date:  2012-09-14       Impact factor: 41.582

9.  Molecular pathways: targeting PARP in cancer treatment.

Authors:  Khanh Do; Alice P Chen
Journal:  Clin Cancer Res       Date:  2012-12-26       Impact factor: 12.531

10.  Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy.

Authors:  Cigall Kadoch; Diana C Hargreaves; Courtney Hodges; Laura Elias; Lena Ho; Jeff Ranish; Gerald R Crabtree
Journal:  Nat Genet       Date:  2013-05-05       Impact factor: 38.330

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  45 in total

1.  Ampullary cancer: Evaluation of somatic and germline genetic alterations and association with clinical outcomes.

Authors:  Winston Wong; Maeve A Lowery; Michael F Berger; Yelena Kemel; Barry Taylor; Ahmet Zehir; Preethi Srinivasan; Chaitanya Bandlamudi; Joanne Chou; Marinela Capanu; Anna Varghese; Kenneth H Yu; Christine A Iacobuzio-Donahue; Jinru Shia; David S Klimstra; William R Jarnagin; Zsofia K Stadler; Eileen M O'Reilly
Journal:  Cancer       Date:  2019-01-08       Impact factor: 6.860

2.  Coordinately Targeting Cell-Cycle Checkpoint Functions in Integrated Models of Pancreatic Cancer.

Authors:  Sejin Chung; Paris Vail; Agnieszka K Witkiewicz; Erik S Knudsen
Journal:  Clin Cancer Res       Date:  2018-12-11       Impact factor: 12.531

3.  Clinical and Genetic Implications of DNA Mismatch Repair Deficiency in Patients With Pancreatic Ductal Adenocarcinoma.

Authors:  Jordan M Cloyd; Matthew H G Katz; Huamin Wang; Amanda Cuddy; Y Nancy You
Journal:  JAMA Surg       Date:  2017-11-01       Impact factor: 14.766

Review 4.  Oncogenic KRAS and the EGFR loop in pancreatic carcinogenesis-A connection to licensing nodes.

Authors:  Christian Schneeweis; Matthias Wirth; Dieter Saur; Maximilian Reichert; Günter Schneider
Journal:  Small GTPases       Date:  2017-01-20

5.  Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer.

Authors:  Erik S Knudsen; Vishnu Kumarasamy; Sejin Chung; Amanda Ruiz; Paris Vail; Stephanie Tzetzo; Jin Wu; Ram Nambiar; Jared Sivinski; Shailender S Chauhan; Mukund Seshadri; Scott I Abrams; Jianmin Wang; Agnieszka K Witkiewicz
Journal:  Gut       Date:  2020-05-18       Impact factor: 23.059

Review 6.  Is it time to split strategies to treat homologous recombinant deficiency in pancreas cancer?

Authors:  Min Yuen Teo; Eileen M O'Reilly
Journal:  J Gastrointest Oncol       Date:  2016-10

7.  Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.

Authors:  Chunling Hu; Steven N Hart; Eric C Polley; Rohan Gnanaolivu; Hermela Shimelis; Kun Y Lee; Jenna Lilyquist; Jie Na; Raymond Moore; Samuel O Antwi; William R Bamlet; Kari G Chaffee; John DiCarlo; Zhong Wu; Raed Samara; Pashtoon M Kasi; Robert R McWilliams; Gloria M Petersen; Fergus J Couch
Journal:  JAMA       Date:  2018-06-19       Impact factor: 56.272

8.  KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes.

Authors:  M Oliverius; D Flasarova; B Mohelnikova-Duchonova; M Ehrlichova; V Hlavac; M Kocik; O Strouhal; P Dvorak; I Ojima; P Soucek
Journal:  Mutagenesis       Date:  2019-12-19       Impact factor: 3.000

Review 9.  Leveraging Mechanisms Governing Pancreatic Tumorigenesis To Reduce Pancreatic Cancer Mortality.

Authors:  Timothy R Donahue; David W Dawson
Journal:  Trends Endocrinol Metab       Date:  2016-07-25       Impact factor: 12.015

10.  An in vivo multiplexed small-molecule screening platform.

Authors:  Barbara M Grüner; Christopher J Schulze; Dian Yang; Daisuke Ogasawara; Melissa M Dix; Zoë N Rogers; Chen-Hua Chuang; Christopher D McFarland; Shin-Heng Chiou; J Mark Brown; Benjamin F Cravatt; Matthew Bogyo; Monte M Winslow
Journal:  Nat Methods       Date:  2016-09-12       Impact factor: 28.547

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