Latest News

• 5th Annual Tumor Takedown Event in Florida!        

  The annual Tumor Takedown fundraiser is coming up this Saturday, May 2nd from 4-7pm at Millennial Brewing Company in Fort Myers, Florida. This event is put on by Zachary, brain tumor survivor and thriver, to raise local awareness of brain cancer. 100% of the donations go to the Musella Foundation to help brain tumor patients through emotional and financial support, education, advocacy and raising money for brain tumor research. For more info, click here! 

  
  
• Evaluation of Regorafenib in Newly Diagnosed and Recurrent Glioblastoma: GBM AGILE Phase II/III Bayesian Randomized Platform Trial        

  The phase 2/3 GBM AGILE platform trial has now reported final results for the regorafenib (Stivarga) arm. In the study, regorafenib was tested in both recurrent glioblastoma (against lomustine) and newly diagnosed unmethylated glioblastoma (against standard chemoradiation). The trial did not find an overall survival benefit in either group, and regorafenib was associated with more toxicity compared to control. These findings are not entirely surprising given the modest survival signal seen in the earlier phase 2 REGOMA trial for recurrent GBM.

  While disappointing, the GBM AGILE platform continues to represent an important advance in GBM drug development by enabling rapid, randomized testing of drug candidates within an adaptive framework, allowing ineffective agents to be deprioritized more efficiently.

  From a broader perspective, these results also reinforce a recurring theme in GBM: monotherapy approaches, particularly with targeted kinase inhibitors, have repeatedly failed to translate early-phase signals into durable clinical benefit. This underscores the need for rational combination strategies that address the multiple redundant resistance pathways that drive GBM progression.

  
  
• IL-6 underlies microenvironment immunosuppression and resistance to therapy in glioblastoma        

  This UCSF preclinical study reaffirms IL-6 as an important regulator of the glioblastoma (GBM) immune tumor microenvironment (TME) and a potential target for combination therapy. Using integrated spatial and single-cell analyses of patient-matched human GBM samples, the authors show that lower baseline IL-6 is associated with the rare clinical responses seen with immune checkpoint inhibitors (ICIs), while higher IL-6 correlates with poorer outcomes. These findings are consistent with prior observations by Dr. Steven Brem and others linking IL-6 to glioma progression, senescence-associated genes, immune suppression and prognosis in GBM.
  
  In the current study by Jacob Young, et al., using preclinical models, IL-6 blockade alone was not sufficient for durable tumor control, but it shifted the tumor immune microenvironment to a more immunoresponsive TME by reducing regulatory T cells, activating dendritic cells, and increasing antigen presentation and effector CD8+ T-cell activity. When combined with immune checkpoint inhibition and radiotherapy, IL-6 blockade translated into more durable anti-tumor responses. This work further supports a combination strategy of targeting cytokine-driven resistance pathways by blocking IL-6, and potentially other immunosuppressive cytokines, to overcome immunotherapy resistance in GBM. Currently, an NRG multicenter trial (NCT04729959), combining anti-IL6R antibody (tocilizumab) with an ICI (atezolizumab) and fractionated radiotherapy has completed accrual and the data is being analyzed. We will share those results when they become available! 

  
  
• Brown Health researchers identify key molecule behind 'exceptional responders' with glioblastoma        

  A new study has identified miR-181d, a naturally occurring microRNA that regulates gene expression, as a potential mediator of glioblastoma (GBM) treatment sensitivity. The study team found that higher miR-181d levels were associated with GBM “exceptional responders,” the rare patients who experience unusually durable responses to therapy.

  The data suggest miR-181d improves treatment response by suppressing multiple resistance pathways. Prior work showed miR-181d suppresses MGMT, a key mediator of temozolomide resistance. In this study, the authors show that miR-181d also suppresses RAD51, a critical DNA repair protein, thereby increasing tumor sensitivity to radiation and other DNA-damage therapy. Lower RAD51 expression in patient tumors was associated with longer survival, consistent with prior reports.

  In preclinical models, intracranial delivery of miR-181d prior to radiation improved tumor control and survival. In an immunocompetent recurrent GBM mouse model, median survival increased from 41 days with radiation alone to 58 days with the addition of miR-181d, with roughly half of treated animals surviving beyond three months. Re-implantation of GBM cells into long-term survivors resulted in lower tumor burden by bioluminescence imaging, consistent with durable anti-tumor immune recognition.

  These findings support the concept that miR-181d may both enhance tumor sensitivity to standard therapy and help sustain anti-tumor immunity. The authors are now working toward a clinical trial evaluating local delivery of miR-181d during surgery.