People of all ages are diagnosed with brain cancer, but there is more frequency among children and older adults. Brain cancer is the second most commonly diagnosed cancer in children (after leukemia).
- Of the nearly 80,000 brain tumors diagnosed in the U.S. each year, approximately 32% are considered malignant – or cancerous.
- An estimated 23,890 malignant tumors of the brain and spinal cord will be diagnosed in the U.S. in 2020, with around 18,020 deaths expected to result from the diagnosis.
- Overall, the chance that a person will develop a malignant tumor of the brain or spinal cord in his or her lifetime is less than 1% (about 1 in 143 for men and 1 in 185 for women).
- Survival rates vary widely depending on the type of tumor.
- Glioblastoma (GBM) is the deadliest type of brain cancer, accounting for 48.3% of all malignant brain tumors and the five-year average survival rate is only 5% or less.
Source: American Cancer Society’s Cancer Facts & Figures 2020 and American Brain Tumor Association’s Brain Tumor Statistics
Brain Cancer Research
In addition to specific projects listed below, genomics research is helping us attack brain cancers – and all types of cancer. NFCR has distinguished itself from other organizations by emphasizing long-term, transformative research and working to move people toward cancer genomics.
Dr. Rakesh Jain a renowned expert in understanding the tumor’s abnormal microenvironment, previously discovered that an imbalance of vessel growth in tumors results in leaky blood vessels (edema), lack of oxygen and immunosuppression. His research is now determining why a new revolutionary immunotherapy is not effective in GBM. In models of GBM, his team discovered the abnormal vessels limit the immune system’s T cells to kill tumors.Treating GBM models with blood vessel growth inhibitors that he previously discovered, led to more normal tumor vessels and improved outcomes when combined with the immunotherapy. Dr. Jain’s research has high potential to improve treatment outcomes and increase survival in GBM patients.
Unlike other cancers, effective treatment options for GBM patients have improved little in recent decades. NFCR has been a pioneer and founding supporter of GBM AGILE clinical trial — a platform different from ‘traditional’ clinical trials in many ways: it can evaluate multiple therapies simultaneously; allow researchers to quickly identify drugs that are showing promising results; and seamlessly transition them to a confirmatory stage designed to support fast drug approval, saving patient’s precious time. NFCR is a strategic partner with the Global Coalition for Adaptive Research (GCAR), the official sponsor of GBM AGILE. In 2019, eleven GBM AGILE trial sites opened in the US and rapid expansion will be available at nearly 40 sites in the US and Canada. We are hopeful that GBM AGILE will serve as a model trial platform that can be applied to other cancers—giving patients hope for treatments that are best suited for their care.
Dr. Paul Fisher discovered IL/24, an immune modulator gene that causes primary and metastatic tumor cells to commit ‘cell suicide’ but leaves healthy cells untouched. IL/24 has multiple anti-cancer effects including sensitizing tumor cells to radiation, chemotherapy and immunotherapy. Dr. Fisher is developing an IL/24 gene therapy that also includes a gene that fluoresces (lights up) when IL/24 locates and destroys tumor cells for a detection- and treatment-monitoring approach (known as theranostics). Another therapy combines IL/24 with a patient’s own immune T cells (adoptive cell therapy) to supercharge T cells to fight cancer even more effectively.
Dr. Fisher and Dr. Web Cavenee have focused lL/24 research for a new treatment for GBM. With support from the NFCR AIM-HI Translational Research Initiative, IL/24 gene therapy will advance soon to a Phase I clinical trial to provide GBM patients hope for a new effective treatment.
Dr. Fisher also discovered the gene, MDA-9/ Syntenin, that promotes the deadly spread (metastasis) of many cancers. Dr. Web Cavenee and he developed an innovative drug called PDZ1i to block the gene’s signals for metastasis. PDZ1i may be effective in treating numerous metastatic cancers. Radiation treatment can induce GBM cells to invade healthy tissue. PDZ1i treatment, in combination with radiation, results in profound survival benefits in pre-clinical models of GBM. With support from the NFCR AIM-HI Translational Research Initiative, the scientists are furthering their research on PDZ1i treatment towards clinical trials to benefit patients.
Brain and other cancers of the central nervous system account for 26% of childhood cancers with medulloblastoma as the most common type. Dr. Cesare Spadoni’s team is focused on developing a therapy with the ‘2Hit approach’ – a compound or combination of agents that attack two or more therapeutic targets in medulloblastoma cancer cells. The 2Hit approach aims to simultaneously increase effectiveness and reduce potential drug resistance. Ongoing research has identified 3 synergistic combinations that inhibit several targets. Next steps with bioinformatics (large sets of biological data) will identify a lead compound against two targets in medulloblastoma models. The team of scientists are hopeful a new treatment for this childhood cancer is on the horizon in the next two years.
NFCR-affiliated scientist Dr. W.K. Alfred Yung focuses his research on drugs that target a gene called PI3K, which is a key factor in about 30% of GBM cases. To identify potential targets for drug development, his team collected glioma stem cells (GSCs) from GBM patients and developed a special panel of cell lines to investigate patterns of resistance to P13K inhibitors. Results from the P13K studies have shown GSCs contain increased levels of Wee-1, a protein that controls cell division and growth. Combination of a P13K inhibitor and a Wee-1 inhibitor resulted in greater inhibition of cell growth and the cancer cells were induced into cell suicide. Similar benefits with this combination treatment were observed in complex GBM tumor models. These findings reveal molecular targets and designs for combination therapies that could lead to new treatments for GBM patients.