Innovative Therapy That “Tricks” and Destroys Cancer Cells
Dr Rohit Bhaskar, PhysioApril 12, 2022
Results from pre-clinical research show iron-like compound holds promise for treating patients with glioblastoma, an aggressive brain cancer.
A novel therapy studied at the Medical College of Wisconsin (MCW) Cancer Center has led to a clinical trial for the treatment of glioblastoma, a rare and aggressive form of brain cancer, yet the most common primary brain tumor in adults.
Despite decades of research globally, only incremental gains have been made to extend or enhance quality of life for patients with glioblastoma. Treatment options are limited and typically include a combination of surgery, radiation therapy, and chemotherapy. Now, a new clinical study open at Froedtert & the Medical College of Wisconsin will evaluate an alternative treatment that is administered orally.
The treatment evolved from years of research led by Christopher Chitambar, MD, and his lab to study iron-dependent processes in cancer biology and the mechanisms by which gallium compounds target iron metabolism and block malignant cell growth. In preclinical studies, Drs. Chitambar and Kathleen Schmainda, PhD, discovered that when administered intravenously, gallium maltolate (GaM) significantly slowed the growth of glioblastoma in a rat brain tumor model. Additional studies showed that GaM, administered orally to glioblastoma-bearing rats, significantly reduced the size of their tumors and prolonged survival.
Advanced MRI shows a 93% reduction in contrast enhancing tumor volume (T1+C: yellow arrow) in one rat responding to GaM treatment. IB’s quantitative Delta T1 (ΔT1) maps allow visualization of “true” tumor enhancement free of confounding blood products. IB’s relative cerebral blood volume (rCBV) noticeably decreased by day 50 (white arrow). IB’s fractional tumor burden maps (FTBs) provide the relative lesion proportions of tumor (red and pink) and non-tumor, necrosis (white). Credit: The Medical College of Wisconsin and Imaging Biometrics
GaM, originally developed by Harvard and Stanford educated scientist Lawrence R. Bernstein, PhD, is an orally available form of the metal gallium, which, in the body, shares many chemical properties with the highly oxidized form of iron, Fe(III). Numerous studies examining the relationship between iron and cancer show that increased levels of iron in the body can be associated with increased cancer risk and severity, due to cancer cells’ dependence on iron to multiply and spread. Because of gallium’s similarity to Fe(III) (the form of iron cancer cells take up), cancer cells take up gallium instead of iron, preventing their multiplication, ultimately leading to their death.
“The discovery that GaM has anticancer activity against glioblastoma in pre-clinical studies is extremely exciting; it opens the door for developing it as a drug for treatment of glioblastoma in patients,” says Christopher Chitambar, MD, Emeritus Professor of Medicine and Biophysics, Division of Hematology and Oncology at MCW. “The anticancer mechanism of GaM applies to other solid tumors as well,” he adds.
Jennifer Connelly, MD, Associate Professor of Neurology at MCW, is Principal Investigator (PI) of the clinical trial with Dr. Chitambar serving as co-PI and Chair. Both are long-standing collaborators with Kathleen Schmainda, PhD, a co-founder of Imaging Biometrics, LLC, and a recognized leader in brain tumor imaging. Dr. Bernstein is participating as a co-investigator.
The trial is being sponsored by Imaging Biometrics, with supporting grants from the Musella Brain Tumor Foundation and the MCW Cancer Center. Based in Elm Grove, WI, Imaging Biometrics is a wholly owned subsidiary of IQ-AI Ltd.
With over a decade of experience in quantitative brain tumor imaging analysis, including analysis for several national multi-center trials, Imaging Biometrics will provide image analysis solutions for evaluating the response to GaM. “We are working with an excellent team of scientists and clinicians, and everyone is eager to move this study forward,” says Michael Schmainda, CEO of Imaging Biometrics.
The trial, being conducted at Froedtert & the Medical College of Wisconsin, is currently accepting participants and has an anticipated completion date of December 2025.
About the Medical College of Wisconsin
With a history dating back to 1893, the Medical College of Wisconsin is dedicated to leadership and excellence in education, patient care, research and community engagement. More than 1,500 students are enrolled in MCW’s medical school and graduate school programs in Milwaukee, Green Bay and Central Wisconsin. MCW’s School of Pharmacy opened in 2017. A major national research center, MCW is the largest research institution in the Milwaukee metro area and second largest in Wisconsin. In the last ten years, faculty received more than $1.6 billion in external support for research, teaching, training and related purposes. This total includes highly competitive research and training awards from the National Institutes of Health (NIH). Annually, MCW faculty direct or collaborate on more than 3,100 research studies, including clinical trials. Additionally, more than 1,650 physicians provide care in virtually every specialty of medicine for more than 4 million patients annually.
ABOUT Imaging Biometrics, LLC
Imaging Biometrics®, a subsidiary of IQ-AI Limited (OTCQB:IQAIF, LON:IQAI), develops and provides visualization and analytical solutions that enable clinicians to better diagnose and treat disease with greater confidence. Through close collaboration with top researchers and clinicians, sophisticated advancements are translated into platform- independent and automated software plug-ins which can extend the base functionality of workstations, imaging systems, PACS, or medical viewers. By design, IB’s advanced visualization software seamlessly integrates into routine workflows.
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