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Abstract C52: A novel combinatorial treatment for glioblastoma of temozolomide and JLK1486
Ist Teil von
Molecular cancer therapeutics, 2013-11, Vol.12 (11_Supplement), p.C52-C52
Erscheinungsjahr
2013
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Abstract
Background: Glioblastoma multiforme (GBM) is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly invasive and resistant to chemotherapeutic treatments. The current standard of care, comprised of surgical resection followed by radiation and chemotherapy, only provides GBM patients with a 12-14 month survival period. Our lab is currently investigating the potential therapeutic combination of temozolomide, the chemotherapeutic agent currently used to treat GBM patients, with a novel agent, JLK1486, to determine if this combination decreases or inhibits tumor recurrence in vitro.
Materials and Methods: GBM neurospheres and primary lines were treated with single or combination treatments of temozolomide (TMZ) and/or JLK1486. Spheres were counted on day 7 to determine initial sphere formation, re-counted on day 14 to determine recovery, and were then pH dissociated and counted on day 21 to determine secondary sphere formation.
Results: Our lab found that neither TMZ nor JLK1486 alone eliminated secondary sphere formation. When cells were treated with a single dose of both TMZ+JLK1486 on day 0 secondary sphere formation was not inhibited. However, when cells where treated with TMZ+JLK1486 on day 0 and then dosed a second time with JLK1486 on day 7, secondary sphere formation was significantly reduced in double versus single agent treated cells. At least part of the enhanced efficacy of TMZ and JLK1486 involves activation of the unfolded protein response (UPR), which in turn increases expression of CHOP and induces apoptosis.
Conclusion: Combining novel chemotherapeutic agents with the current standard of chemotherapeutic care, TMZ, may not only inhibit tumor growth but also tumor recurrence. Our lab found that when a novel chemotherapeutic agent, JLK1486, was combined with TMZ, secondary sphere formation was inhibited, suggesting that dual treatment is more efficacious than single agent in inhibiting secondary sphere formation and may reduce tumor recurrence. Combined therapy of UPR-inducing agents with chemotherapy is a promising approach to enhance efficacy by eliminating the few surviving cells that allow formation of secondary spheres and, perhaps, tumor recurrence.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C52.
Citation Format: Jessica L. Weatherbee, Jean-Louis Kraus, Richard P. Moser, Alonzo H. Ross. A novel combinatorial treatment for glioblastoma of temozolomide and JLK1486. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C52.