CROGEN Pharmaceuticals

Founders: Carlo M. Croce, M.D. and Sidney Kimmel

CROGEN Pharmaceueuticals is a molecular target/drug development company that exploits the consistent genetic changes observed in human cancer, to verify the importance of these changes in the initiation and progression of liquid and solid malignancies and to develop new diagnostic, preventive and therapeutic approaches and pharmaceuticals for human cancers.  The company has licenses for several tumor suppressor genes involved in the majority of human cancers such as FHIT and FEZ/LZTS1 and several oncogenes such as TCL1 and for mouse models of human cancers where these genes have been altered.  The company is also the pioneer in studies of the role of microRNA genes in human malignancies and in the development of microRNA gene chips and microRNA directed pharmaceuticals.

 

The Science:

Calin GA, Croce CM. Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin Oncol. 2006 Apr;33(2):167-73.. ( Abstract )

Garzon R, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R, Volinia S, Bhatt D, Alder H, Marcucci G, Calin GA, Liu CG, Bloomfield CD, Andreeff M, Croce CM. MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5078-83. Epub 2006 Mar 20. ( Abstract )

Fedele M, Fidanza V, Battista S, Pentimalli F, Klein-Szanto AJ, Visone R, De Martino I, Curcio A, Morisco C, Del Vecchio L, Baldassarre G, Arra C, Viglietto G, Indolfi C, Croce CM, Fusco A. Haploinsufficiency of the Hmga1 gene causes cardiac hypertrophy and myelo-lymphoproliferative disorders in mice. Cancer Res. 2006 Mar 1;66(5):2536-43. ( Abstract )

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61. Epub 2006 Feb 3. ( Abstract )

Zanesi N, Aqeilan R, Drusco A, Kaou M, Sevignani C, Costinean S, Bortesi L, La Rocca G, Koldovsky P, Volinia S, Mancini R, Calin G, Scott CP, Pekarsky Y, Croce CM. Effect of rapamycin on mouse chronic lymphocytic leukemia and th development of nonhematopoietic malignancies in Emu-TCL1 transgenic mice. Cancer Res. 2006 Jan 15;66(2):915-20. ( Abstract )

Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM, Pekarsky Y. Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. Cancer Res. 2005 Dec 15;65(24):11282-6. ( Abstract )

Calin GA, Garzon R, Cimmino A, Fabbri M, Croce CM. MicroRNAs and leukemias: how strong is the connection. Leuk Res. 2006 Jun;30(6):653-5. Epub 2005 Dec 2. ( Abstract )

Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chroni lymphocytic leukemia. N Engl J Med. 2005 Oct 27;353(17):1793-801. ( Abstract )

Fabbri M, Iliopoulos D, Trapasso F, Aqeilan RI, Cimmino A, Zanesi N, Yendamuri S, Han SY, Amadori D, Huebner K, Croce CM. WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15611-6. Epub 2005 Oct 13. ( Abstract )

Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13944-9. Epub 2005 Sep 15. ( Abstract )

Liu CG, Zhang L, Jiang Y, Chatterjee D, Croce CM, Huebner K, Fong LY. Modulation of gene expression in precancerous rat esophagus by dietary zinc deficit and replenishment. Cancer Res. 2005 Sep 1;65(17):7790-9. ( Abstract )

Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005 Aug 15;65(16):7065-70. ( Abstract )

Zanesi N, Pekarsky Y, Croce CM. A mouse model of the fragile gene FHIT: From carcinogenesis to gene therapy and cancer prevention. Mutat Res. 2005 Dec 11;591(1-2):103-9. Epub 2005 Aug 8. ( Abstract )

Aqeilan RI, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarsky Y, Sudol M, Croce CM. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 2005 Aug 1;65(15):6764-72. ( Abstract )\

Zanesi N, Mancini R, Sevignani C, Vecchione A, Kaou M, Valtieri M, Calin GA, Pekarsky Y, Gnarra JR, Croce CM, Huebner K. Lung cancer susceptibility in Fhit-deficient mice is increased by Vh haploinsufficiency. Cancer Res. 2005 Aug 1;65(15):6576-82. ( Abstract )

Drusco A, Zanesi N, Roldo C, Trapasso F, Farber JL, Fong LY, Croce CM. Knockout mice reveal a tumor suppressor function for Testin. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10947-51. Epub 2005 Jul 20. ( Abstract )

Croce CM, Calin GA. miRNAs, cancer, and stem cell division. Cell. 2005 Jul 15;122(1):6-7. ( Abstract )

Calin GA, Trapasso F, Shimizu M, Dumitru CD, Yendamuri S, Godwin AK, Ferracin M, Bernardi G, Chatterjee D, Baldassarre G, Rattan S, Alder H, Mabuchi H, Shiraishi T, Hansen LL, Overgaard J, Herlea V, Mauro FR, Dighiero G, Movsas B, Rassenti L, Kipps T, Baffa R, Fusco A, Mori M, Russo G, Liu CG, Neuberg D, Bullrich F, Negrini M, Croce CM. Familial cancer associated with a polymorphism in ARLTS1. N Engl J Med. 2005 Apr 21;352(16):1667-76. ( Abstract )

Garzon R, Croce CM. MicroRNAs in normal and malignant hematopoiesis. Curr Opin Hematol. 15(4):352-8, 2008. ( Abstract )

Aqeilan RI, Hassan MQ, de Bruin A, Hagan JP, Volinia S, Palumbo T, Hussain S, Lee SH, Gaur T, Stein GS, Lian JB, Croce CM. The WWOX tumor suppressor is essential for post-natal survival and normal bone metabolism. J Biol Chem. 2008 May 16; [Epub ahead of print]. ( Abstract )

Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, Liu CG, Giannakakis A, Alexiou P, Hasegawa K, Johnstone CN, Megraw MS, Adams S, Lassus H, Huang J, Kaur S, Liang S, Sethupathy P, Leminen A, Simossis VA, Sandaltzopoulos R, Naomoto Y, Katsaros D, Gimotty PA, DeMichele A, Huang Q, Bützow R, Rustgi AK, Weber BL, Birrer MJ, Hatzigeorgiou AG, Croce CM, Coukos G. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A. 105(19):7004-9, 2008. ( Abstract )

Marcucci G, Radmacher MD, Maharry K, Mrózek K, Ruppert AS, Paschka P, Vukosavljevic T, Whitman SP, Baldus CD, Langer C, Liu CG, Carroll AJ, Powell BL, Garzon R, Croce CM, Kolitz JE, Caligiuri MA, Larson RA, Bloomfield CD. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med. 358(18):1919-28, 2008. ( Abstract )

Liu CG, Calin GA, Volinia S, Croce CM. MicroRNA expression profiling using microarrays. Nat Protoc. 3(4):563-78, 2008. ( Abstract )

Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 105(13):5166-71, 2008. ( Abstract )

Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, Volinia S, Liu CG, Schnittger S, Haferlach T, Liso A, Diverio D, Mancini M, Meloni G, Foa R, Martelli MF, Mecucci C, Croce CM, Falini B. Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A. 105(10):3945-50, 2008. ( Abstract )

Fabbri M, Croce CM, Calin GA. MicroRNAs. Cancer J. 14(1):1-6, 2008. ( Abstract )

Croce CM. Oncogenes and cancer. N Engl J Med. 358(5):502-11, 2008. ( Abstract )

Garzon R, Volinia S, Liu CG, Fernandez-Cymering C, Palumbo T, Pichiorri F, Fabbri M, Coombes K, Alder H, Nakamura T, Flomenberg N, Marcucci G, Calin GA, Kornblau SM, Kantarjian H, Bloomfield CD, Andreeff M, Croce CM. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood. 111(6):3183-9, 2008. ( Abstract )