In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 1085-1085
Abstract:
Gliomas are the most common primary tumors affecting the adult human Central Nervous System (CNS). The most lethal is grade IV glioblastoma (GBM), which gives a median survival of only 15 months, but less severe grades also respond poorly to standard therapy. Myc is a bHLHZip transcription factor, causally implicated in most human tumors. In the past, we employed a dominant negative of Myc transactivation activity, termed Omomyc, and we showed that Myc inhibition is a potent strategy in cancer therapy, both in K-RasG12D-driven lung tumors and in T antigen-driven pancreatic β-cell insulinomas. Now, we make use of a mouse model of Ha-Ras driven glioma coupled with our Omomyc switchable model in order to assess Myc inhibition as a therapeutic strategy in glioma. Myc inhibition has a dramatic therapeutic impact in the animals, being able to both prevent formation and cause regression of tumors. We also tested neuroprogenitor cells derived from the same animal model as putative cells of origin of glioma. In this context, Myc inhibition reduced proliferation, increased death and impaired the self-renewal of Ha-Ras transformed neuroprogenitors. Similar results were obtained with human glioblastoma cell lines, which presented severe mitotic catastrophe as a consequence of Omomyc expression, revealing a new Achilles’ heel of glioblastoma. Finally, Myc inhibition was tested in orthotopic xenografts using patient-derived tumor samples and showed once again dramatic therapeutic impact, conferring a significant survival advantage to recipient animals. Conclusion: Myc inhibition is a potent therapeutic strategy in glioma and its effects include induction of mitotic crisis in tumor cells. Citation Format: Daniela Annibali, Jonathan R. Whitfield, Emilia Favuzzi, Toni Jauset, Erika serrano, Gerard Folch, Marta I. Cuartas, Alba Gonzalez, Lamorna Brown Swigart, Sergio Nasi, Gerard I. Evan, Joan Seoane, Laura Soucek. MYC inhibition is a potent therapy against glioma and induces mitotic crisis in cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1085. doi:10.1158/1538-7445.AM2013-1085
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-1085
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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