Gastrointestinal Malignancies Program

The DF/HCC Gastrointestinal Malignancies Program (GI Program) fosters research to unravel the pathophysiology of GI cancers and to design and implement novel strategies for early diagnosis, more effective and accurate treatment, and prevention. The program has made important advances that have translated into a robust portfolio of clinical trials using novel, rationally designed agents with broad consensus and participation across all DF/HCC institutions.

The GI Program has established a culture of inter-institutional communication and collaboration uniting more than 80 basic, translational, clinical, and population scientists, representing all biomedical disciplines. Given the complexity and heterogeneity of GI malignancies, the program has historically emphasized pancreatic and colorectal cancers, two of the four leading causes of U.S. cancer deaths. The Program is intensifying efforts in hepatobiliary, esophagogastric, and neuroendocrine tumors. Currently, the Program has more than 90 members.

Recent Publications

  • Fitamant J, Kottakis F, Benhamouche S, Tian HS, Chuvin N, Parachoniak CA, Nagle JM, Perera RM, Lapouge M, Deshpande V, Zhu AX, Lai A, Min B, Hoshida Y, Avruch J, Sia D, Campreciós G, McClatchey AI, Llovet JM, Morrissey D, Raj L, Bardeesy N. YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression. Cell Rep 2015. PubMed
  • Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T, Clayton KL, Raab M, Chen Q, Beauchemin N, Yazaki PJ, Pyzik M, Ostrowski MA, Glickman JN, Rudd CE, Ploegh HL, Franke A, Petsko GA, Kuchroo VK, Blumberg RS. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 2015; 517:386-90. PubMed
  • Giannakis M, Hodis E, Jasmine Mu X, Yamauchi M, Rosenbluh J, Cibulskis K, Saksena G, Lawrence MS, Qian ZR, Nishihara R, Van Allen EM, Hahn WC, Gabriel SB, Lander ES, Getz G, Ogino S, Fuchs CS, Garraway LA. RNF43 is frequently mutated in colorectal and endometrial cancers. Nat Genet 2014; 46:1264-6. PubMed
  • Mayers JR, Wu C, Clish CB, Kraft P, Torrence ME, Fiske BP, Yuan C, Bao Y, Townsend MK, Tworoger SS, Davidson SM, Papagiannakopoulos T, Yang A, Dayton TL, Ogino S, Stampfer MJ, Giovannucci EL, Qian ZR, Rubinson DA, Ma J, Sesso HD, Gaziano JM, Cochrane BB, Liu S, Wactawski-Wende J, Manson JE, Pollak MN, Kimmelman AC, Souza A, Pierce K, Wang TJ, Gerszten RE, Fuchs CS, Vander Heiden MG, Wolpin BM. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 2014; 20:1193-8. PubMed
  • Ting DT, Wittner BS, Ligorio M, Vincent Jordan N, Shah AM, Miyamoto DT, Aceto N, Bersani F, Brannigan BW, Xega K, Ciciliano JC, Zhu H, MacKenzie OC, Trautwein J, Arora KS, Shahid M, Ellis HL, Qu N, Bardeesy N, Rivera MN, Deshpande V, Ferrone CR, Kapur R, Ramaswamy S, Shioda T, Toner M, Maheswaran S, Haber DA. Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep 2014; 8:1905-18. PubMed
  • Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, Hinoue T, Laird PW, Curtis C, Shen H, Weisenberger DJ, Schultz N, Shen R, Weinhold N, Kelsen DP, Bowlby R, Chu A, Kasaian K, Mungall AJ, Robertson AG, Sipahimalani P, Cherniack AD, Getz G, Liu Y, Noble MS, Pedamallu C, Sougnez C, Taylor-Weiner A, Akbani R, Lee JS, Liu W, Mills GB, Yang D, Zhang W, Pantazi A, Parfenov M, Gulley M, Piazuelo MB, Schneider BG, Kim J, Boussioutas A, Sheth M, Demchok JA, Rabkin CS, Willis JE, Ng S, Garman K, Beer DG, Pennathur A, Raphael BJ, Wu HT, Odze R, Kim HK, Bowen J, Leraas KM, Lichtenberg TM, Weaver S, McLellan M, Wiznerowicz M, Sakai R, Getz G, Sougnez C, Lawrence MS, Cibulskis K, Lichtenstein L, Fisher S, Gabriel SB, Lander ES, Ding L, Niu B, Ally A, Balasundaram M, Birol I, Bowlby R, Brooks D, Butterfield YS, Carlsen R, Chu A, Chu J, Chuah E, Chun HJ, Clarke A, Dhalla N, Guin R, Holt RA, Jones SJ, Kasaian K, Lee D, Li HA, Lim E, Ma Y, Marra MA, Mayo M, Moore RA, Mungall AJ, Mungall KL, Ming Nip K, Robertson AG, Schein JE, Sipahimalani P, Tam A, Thiessen N, Beroukhim R, Carter SL, Cherniack AD, Cho J, Cibulskis K, DiCara D, Frazer S, Fisher S, Gabriel SB, Gehlenborg N, Heiman DI, Jung J, Kim J, Lander ES, Lawrence MS, Lichtenstein L, Lin P, Meyerson M, Ojesina AI, Sekhar Pedamallu C, Saksena G, Schumacher SE, Sougnez C, Stojanov P, Tabak B, Taylor-Weiner A, Voet D, Rosenberg M, Zack TI, Zhang H, Zou L, Protopopov A, Santoso N, Parfenov M, Lee S, Zhang J, Mahadeshwar HS, Tang J, Ren X, Seth S, Yang L, Xu AW, Song X, Pantazi A, Xi R, Bristow CA, Hadjipanayis A, Seidman J, Chin L, Park PJ, Kucherlapati R, Akbani R, Ling S, Liu W, Rao A, Weinstein JN, Kim SB, Lee JS, Lu Y, Mills G, Laird PW, Hinoue T, Weisenberger DJ, Bootwalla MS, Lai PH, Shen H, Triche T Jr, Van Den Berg DJ, Baylin SB, Herman JG, Getz G, Chin L, Liu Y, Murray BA, Noble MS, Askoy BA, Ciriello G, Dresdner G, Gao J, Gross B, Jacobsen A, Lee W, Ramirez R, Sander C, Schultz N, Senbabaoglu Y, Sinha R, Sumer SO, Sun Y, Weinhold N, Thorsson V, Bernard B, Iype L, Kramer RW, Kreisberg R, Miller M, Reynolds SM, Rovira H, Tasman N, Shmulevich I, Ng S, Haussler D, Stuart JM, Akbani R, Ling S, Liu W, Rao A, Weinstein JN, Verhaak RG, Mills GB, Leiserson MD, Raphael BJ, Wu HT, Taylor BS, Black AD, Bowen J, Carney JA, Gastier-Foster JM, Helsel C, Leraas KM, Lichtenberg TM, McAllister C, Ramirez NC, Tabler TR, Wise L, Zmuda E, Penny R, Crain D, Gardner J, Lau K, Curely E, Mallery D, Morris S, Paulauskis J, Shelton T, Shelton C, Sherman M, Benz C, Lee JH, Fedosenko K, Manikhas G, Potapova O, Voronina O, Belyaev D, Dolzhansky O, Rathmell WK, Brzezinski J, Ibbs M, Korski K, Kycler W, Laźniak R, Leporowska E, Mackiewicz A, Murawa D, Murawa P, Spychała A, Suchorska WM, Tatka H, Teresiak M, Wiznerowicz M, Abdel-Misih R, Bennett J, Brown J, Iacocca M, Rabeno B, Kwon SY, Penny R, Gardner J, Kemkes A, Mallery D, Morris S, Shelton T, Shelton C, Curley E, Alexopoulou I, Engel J, Bartlett J, Albert M, Park DY, Dhir R, Luketich J, Landreneau R, Janjigian YY, Kelsen DP, Cho E, Ladanyi M, Tang L, McCall SJ, Park YS, Cheong JH, Ajani J, Camargo MC, Alonso S, Ayala B, Jensen MA, Pihl T, Raman R, Walton J, Wan Y, Demchok JA, Eley G, Mills Shaw KR, Sheth M, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Davidsen T, Hutter CM, Sofia HJ, Burton R, Chudamani S, Liu J. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014. PubMed
  • Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Canzian F, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Jacobs EJ, Kamineni A, Klein AP, Kolonel LN, Kulke MH, Li D, Malats N, Olson SH, Risch HA, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Austin MA, Barfield R, Basso D, Berndt SI, Boutron-Ruault MC, Brotzman M, Büchler MW, Bueno-de-Mesquita HB, Bugert P, Burdette L, Campa D, Caporaso NE, Capurso G, Chung C, Cotterchio M, Costello E, Elena J, Funel N, Gaziano JM, Giese NA, Giovannucci EL, Goggins M, Gorman MJ, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Henderson BE, Holly EA, Hu N, Hunter DJ, Innocenti F, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, LaCroix A, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Nakamura Y, Oberg AL, Owzar K, Patel AV, Peeters PH, Peters U, Pezzilli R, Piepoli A, Porta M, Real FX, Riboli E, Rothman N, Scarpa A, Shu XO, Silverman DT, Soucek P, Sund M, Talar-Wojnarowska R, Taylor PR, Theodoropoulos GE, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vodicka P, Wactawski-Wende J, Wentzensen N, Wu C, Yu H, Yu K, Zeleniuch-Jacquotte A, Hoover R, Hartge P, Fuchs C, Chanock SJ, Stolzenberg-Solomon RS, Amundadottir LT. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 2014; 46:994-1000. PubMed
  • Morris SA, Cahan P, Li H, Zhao AM, San Roman AK, Shivdasani RA, Collins JJ, Daley GQ. Dissecting engineered cell types and enhancing cell fate conversion via CellNet. Cell 2014; 158:889-902. PubMed
  • Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RT, Blanc JF, Vogel A, Chen CL, Dorval E, Peck-Radosavljevic M, Santoro A, Daniele B, Furuse J, Jappe A, Perraud K, Anak O, Sellami DB, Chen LT. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 2014; 312:57-67. PubMed
  • Saha SK, Parachoniak CA, Ghanta KS, Fitamant J, Ross KN, Najem MS, Gurumurthy S, Akbay EA, Sia D, Cornella H, Miltiadous O, Walesky C, Deshpande V, Zhu AX, Hezel AF, Yen KE, Straley KS, Travins J, Popovici-Muller J, Gliser C, Ferrone CR, Apte U, Llovet JM, Wong KK, Ramaswamy S, Bardeesy N. Mutant IDH inhibits HNF-4留 to block hepatocyte differentiation and promote biliary cancer. Nature 2014. PubMed
  • Zhou J, Hayakawa Y, Wang TC, Bass AJ. RhoA mutations identified in diffuse gastric cancer. Cancer Cell 2014; 26:9-11. PubMed
  • Wang Y, Marino-Enriquez A, Bennett RR, Zhu M, Shen Y, Eilers G, Lee JC, Henze J, Fletcher BS, Gu Z, Fox EA, Antonescu CR, Fletcher CD, Guo X, Raut CP, Demetri GD, van de Rijn M, Ordog T, Kunkel LM, Fletcher JA. Dystrophin is a tumor suppressor in human cancers with myogenic programs. Nat Genet 2014; 46:601-6. PubMed
  • Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 2014. PubMed
  • Fink SP, Yamauchi M, Nishihara R, Jung S, Kuchiba A, Wu K, Cho E, Giovannucci E, Fuchs CS, Ogino S, Markowitz SD, Chan AT. Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD). Sci Transl Med 2014; 6:233re2. PubMed
  • Maynard MA, Marino-Enriquez A, Fletcher JA, Dorfman DM, Raut CP, Yassa L, Guo C, Wang Y, Dorfman C, Feldman HA, Frates MC, Song H, Jugo RH, Taguchi T, Hershman JM, Larsen PR, Huang SA. Thyroid hormone inactivation in gastrointestinal stromal tumors. N Engl J Med 2014; 370:1327-34. PubMed
  • Nissim S, Sherwood RI, Wucherpfennig J, Saunders D, Harris JM, Esain V, Carroll KJ, Frechette GM, Kim AJ, Hwang KL, Cutting CC, Elledge S, North TE, Goessling W. Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Dev Cell 2014; 28:423-37. PubMed
  • Kim TH, Li F, Ferreiro-Neira I, Ho LL, Luyten A, Nalapareddy K, Long H, Verzi M, Shivdasani RA. Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity. Nature 2014; 506:511-5. PubMed
  • San Roman AK, Jayewickreme CD, Murtaugh LC, Shivdasani RA. Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo. Stem Cell Reports 2014; 2:127-34. PubMed
  • Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J, . Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014; 383:31-9. PubMed
  • Baker K, Rath T, Flak MB, Arthur JC, Chen Z, Glickman JN, Zlobec I, Karamitopoulou E, Stachler MD, Odze RD, Lencer WI, Jobin C, Blumberg RS. Neonatal Fc receptor expression in dendritic cells mediates protective immunity against colorectal cancer. Immunity 2013; 39:1095-107. PubMed
  • Ogino S, Liao X, Imamura Y, Yamauchi M, McCleary NJ, Ng K, Niedzwiecki D, Saltz LB, Mayer RJ, Whittom R, Hantel A, Benson AB, Mowat RB, Spiegelman D, Goldberg RM, Bertagnolli MM, Meyerhardt JA, Fuchs CS, . Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial. Journal of the National Cancer Institute 2013; 105:1789-98. PubMed
  • Bao Y, Han J, Hu FB, Giovannucci EL, Stampfer MJ, Willett WC, Fuchs CS. Association of nut consumption with total and cause-specific mortality. N Engl J Med 2013; 369:2001-11. PubMed
  • Wolpin BM, Bao Y, Qian ZR, Wu C, Kraft P, Ogino S, Stampfer MJ, Sato K, Ma J, Buring JE, Sesso HD, Lee IM, Gaziano JM, McTiernan A, Phillips LS, Cochrane BB, Pollak MN, Manson JE, Giovannucci EL, Fuchs CS. Hyperglycemia, insulin resistance, impaired pancreatic 硫-cell function, and risk of pancreatic cancer. Journal of the National Cancer Institute 2013; 105:1027-35. PubMed
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