Ian F. Pollack, MD

Dr. Pollack’s group has continued to evaluate the role of molecularly targeted therapies for childhood brain tumors with different patterns of genomic alterations. Using pharmacological screening strategies, they have identified agents and agent combinations that had synergistic activity in inhibiting the growth of high-grade and brainstem gliomas. Recognizing that responses to such agents are often transitory in these highly aggressive tumors, they have developed a series of “drug-resistance” tumor model systems, paired with treatment naïve counterparts. They have leveraged this unique resource to built a strong collaboration with the Drug Discovery Institute and the Systems Biology Program, through which they have characterized a heretofore unrecognized mechanism by which pediatric and adult gliomas develop resistance to initially active agents or agent combinations. Using siRNA and pharmacological inhibition, they have demonstrated ways in which this inhibition can be counteracted, which may hold promise for new therapeutic strategies for these tumors. At present, Dr. Pollack’s group is working to validate the generalizability of our observations in different molecularly defined glioma models and with different therapeutic agents, to determine if resistance relies on a common signaling pathway or is the product of different pathways in different tumors in response to different agents. Their preliminary observations suggest the former, which opens a wide niche for therapeutic development. Accordingly, they plan to pursue these in vitro observations in in vivo model systems over the coming year. 

Dr. Pollack’s group has also continued their NIH-funded activities that focus on immunotherapy for pediatric brain tumors. During the last year, they applied RNA sequencing of peripheral blood mononuclear cells in a low-grade glioma cohort to characterize gene expression patterns associated with favorable response to vaccine therapy. They also identified expression patterns that were associated with lack of response. Future efforts will be directed at examining whether these response-associated expression patterns are observed in high-grade glioma and ependymoma cohorts, or are unique to low-grade gliomas. Accrual continues on their ongoing clinical trials for recurrent low-grade gliomas and ependymomas.