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Rutgers Cancer Institute researchers target aggressive brain tumors

NJBIZ - 4/8/2019

Rapidly growing brain tumors known as glioblastoma multiforme (GBM) often present treatment challenges due to their diverse tumor cell types and their ability to spread into healthy brain tissue.
Dr. Hatem Sabaawy, a resident member of Rutgers Cancer Institute of New Jersey, is the senior investigator on research examining the impact of a novel small molecule inhibitor in the treatment of GBM, using a patient’s own tumor cells with patient-derived organoids.
The work is being presented Tuesday at the American Association for Cancer Research Annual Meeting being held in Atlanta.
Sabaawy, who is also a member of the Clinical Investigations and Precision Therapeutics Program at Rutgers Cancer Institute and an associate professor of medicine at Rutgers Robert Wood Johnson Medical School, said that the fact that GBM is the most common and deadly primary brain tumor is what prompted his lab to focus on this type of brain tumor.
"GBMs are thought to derive from neuroglial stem or progenitor cells. At our partner hospital, Robert Wood Johnson University Hospital, an RWJBarnabas Health facility, GBM patients may undergo surgery at RWJUH, then receive radiotherapy and concomitant or alternating chemotherapy," said Sabaaway.
He said that this treatment could be followed by anti-angiogenic therapy, yet, these aggressive GBMs almost always rapidly recur. Despite the advances in genomic medicine, individually tailored strategies based on tumor-intrinsic dominant genomic, epigenomic and antigenic tumor profiles are unavailable even though they may ultimately improve outcomes.
Through a collaboration with neurosurgeon Dr. Shabbar Danish, director, of the RWJ Gamma Knife Center, Sabaaway said that they can take surgical glioblastoma tissues removed from consented GBM patients and derive a new technology in the laboratory to generate patient-derived organoids. "With these organoids, we can then discover and validate new small molecule inhibitors for targeted therapy against GBMs from each patient," said Sabaaway. He also said that the results would help in advancing cancer treatment for this tumor type.
"We now have novel RU-A compounds with favorable features. These include the ability to reduce intratumor BMI1 associated with elimination of the stem cell-like phenotypes, and the lack of any detectable toxicity. Together these are desired features for developing GBM therapy, further suggesting that this series of compounds could be rapidly transitioned to clinical trials."
Sabaaway said that the RU-A compounds offer effective targeted agents that could be utilized alone or combined with other targeted and immune modulatory agents in GBM clinical trials. Also, the novel compounds and patient-derived organoid platform allow the teams at RWJUH and Rutgers Cancer Institute to examine combination therapy and design individualized therapeutic strategies for GBM that relies on utilizing tailored combinations of targeted genetic-, epigenetic- and/or immune-modulating therapies.
"The combination approach when examined in planned clinical trials would have the highest potential to generate effective therapies for GBM."

CREDIT: Anthony Vecchione

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