Lars Hammarstrom to Speak at Cell Based Assay Conference, Oct. 7-8, 2014, Dublin
Lars Hammarström, Karolinska Institutet, to Speak at Cell Based Assay & Screening Technologies Conference, October 7-8, 2014 in Dublin, Ireland.
- (1888PressRelease) July 08, 2014 - Lars Hammarström will speak on "Phenotypic Targeting of Acquired Vulnerabilities in Glioblastoma Multiforme" at the Cell Based Assay & Screening Technologies Conference, to be held October 7-8, 2014 in Dublin, Ireland.
Glioblastoma multiforme (GBM) is the most aggressive of tumors that affect the CNS, and GBM patients have marginal life expectancy. Current treatment options are limited and tumor recurrence frequent, and due to the diverse genetic landscape of gliomas, the success of targeted therapies focusing on specific tumor-driving mutations has been disappointing. Dr. Hammarström, Senior Scientist and co-founder of the Chemical Biology Consortium Sweden at Karolinska Institutet, will share about his group's work in developing a novel method for identifying treatments for GBM.
Assuming that mutations in GBM lead to acquired cellular functions not only involved in the tumorigenic process, the group performed an unbiased phenotypic screen of a small molecule library on patient-derived, tumor-initiating GBM cells to identify specific cellular responses which could be selectively modulated by small molecules. An identified quinoline derivative and subsequent synthesized analogs (termed Vacquinols) reliably compromised GBM viability through a non-apoptotic mechanism associated with massive induction of macropinocytosis which was not induced in other cell types investigated. Though the primary pharmacological target remains unknown, shRNA-induced Vacquinol-1-resistant mutants revealed the MAP-kinase MKK4 as a critical signaling node. Vacquinol-1 displays excellent in vitro and in vivo pharmacokinetics with good exposure into the CNS. Oral administration in a mouse xenograft model of GBM dramatically reduces tumor size, attenuates disease progression and significantly prolongs survival.
Dr. Hammarström will describe current efforts focused on further advancing the Vacquinol series towards clinical development, approaches towards identification of the primary target(s) of Vacquinol-1, and elucidation of the underlying cellular pathways involved in the response.
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