Annual Neuro-Tumor Club Meeting Recap
The 20th Annual Neuro-Tumor Club Meeting took place on April 7, 2014, in San Diego, California. This meeting, for brain tumor researchers attending the AACR Annual Meeting, was organized by the Society for Neuro-Oncology with the support of Genentech, Novocure and the National Brain Tumor Society. Frank Furnari of the Ludwig Institute for Cancer Research, University of California, San Diego, and Shi-Yuan Cheng of Northwestern University, served as co-chairs for the dinner.
The event drew approximately 200 investigators from diverse disciplines relevant to brain tumor research, and was very successful in strengthening existing personal research connections and collaborations, generating new associations and presenting the group with updates in topics important to brain tumor research.
Forty abstracts were received of uniformly high quality. Submissions came from eight countries and were reflective of cutting edge, thought-provoking basic and translational research in the field of neuro-oncology. Trying to reduce this to fourteen talks was difficult given the standard of the submissions. The talks were arranged in four consecutive sessions that encompassed the following topic areas:
• Genomic Phenotyping and Personalized/Combinatorial Therapy
• Tumor Microenvironment, Signaling and Cancer Stem Cells
• Novel Agents, Markers and Immunotherapy
• Animal Models and CNS Metastases
Each topic area was excellently framed by over-views from authority figures in those areas including: Dr. Richard Gilbertson, St. Jude Children's Research Hospital; Albert Wong, Stanford University; Isabella Taylor, Johns Hopkins University; and Carol Kruse, University of California, Los Angeles.
The meeting took place at the Hotel Solamar, located near the 2014 Annual AACR Meeting venue. The 14 speakers were scheduled over three hours, requiring a tight time-line, which was kept judiciously by all presenters. All speakers managed to finish on time and yet conveyed an astonishing amount of background information and experimental data. The talks were followed by lively discussions. There were many excellent presentations during the night. In the first session, Richard Gilbertson presented data derived from whole genome and RNA sequencing of supratentorial ependymomas showing a highly recurrent oncogenic fusion occurring between RELA and an uncharacterized gene, C11orf95, in 70% of these tumors. Expression of the C11orf95-RELA fusion protein in neural stem cells drove their transformation in conjunction with an oncogenic NF-B transcription signature, raising the possibility of new avenues for therapeutic intervention.
In the next session, Albert Wong showed that the mutant EGF receptor, EGFRvIII, is frequently co-expressed with the stem cell marker, CD133, and that EGFRvIII+/CD133+ tumor cells were highly aggressive. Targeting these double positive cells with a bi-specific monoclonal antibody greatly enhanced survival of tumor-bearing mice. Also in this session, Terry Johns showed that extracellular domain mutants of EGFR found in glioma are more sensitive to the pan-ErbB inhibitor, dacomitininb, when compared to the wild type receptor, and that Ras mutations cause up front resistance to EGFR based therapy. In session three, Chien-Tsun Kuan provided updates on the development of recombinant immunotoxins (RITs) that target wild type EGFR and EGFRvIII on the surface of glioma cells and a new surface marker for gliomas, glycoprotein NMB. He also described new approaches of reducing immunogenicity of these RITs in humans and the next generation of RIT. Elizabeth Maher reported detection of 2HG by MR spectroscopy, which proved to be a robust clinical biomarker in low-grade gliomas. The initial success of using 2HG levels to guide therapies for gliomas, especially for these low-grade gliomas, was highly encouraging. The final session had four excellent presentations that described studies using various animal models of brain tumors to demonstrate the role of ATRX in glioma progression and response to DNA damage, initial characterization of a new de novo animal model of leptomenigeal metastasis, combination of cellular and gene therapies to treat breast cancer patients with brain metastasis, and deciphering circulating tumor cells from patients with breast cancer metastatic to the brain. The evening concluded with many of the attendees remaining to engage in informal conversation prompted by the presented topics.
The Society thanks Drs. Furnari and Cheng for organizing a stimulating and enjoyable evening. SNO members are encouraged to mark their calendars for the next Neuro-Tumor Club Dinner, scheduled to take place on Monday, April 20, 2015 in Philadelphia, PA.