In 2025, the NIH’s National Cancer Institute estimates that there will be approximately 24,820 new brain cancer cases and 18,330 deaths from the disease in the United States. Tumors of the brain and spinal cord, which comprise the central nervous system (CNS), come in many forms. These tumors in this system can either be benign (non-cancerous) or malignant (cancerous).

Controlling critical physiological and cognitive functions, the brain is divided into three parts:

• Cerebrum: Located at the top of the head, this part manages thinking, memory, emotions, speech, reading, writing and voluntary movement.
• Cerebellum: Located at the lower back of the brain, this part regulates coordination, balance and posture.
• Brain Stem: Located at the base of the brain, just above the neck, this part connects the brain to the spinal cord and controls automatic functions such as breathing and heart rate. This part also manages nerves and muscles involved in vision, hearing, speech and swallowing.

  The spinal cord is a column of nerve tissue that runs from the brain stem down the center of the back and connects the brain to nerves in most parts of the body.

The spinal cord is surrounded by three protective membranes and encased by the vertebrae — the bones of the spine and serves as a communication pathway, sending signals from the brain to the body to control movements and receiving sensory information from the body to send to the brain.

Tumors that originate in the brain are known as primary brain tumors. While they can spread within the brain or to the spine, they rarely spread beyond the central nervous system (CNS). In contrast, some brain tumors originate from cancer elsewhere in the body and then spread to the brain. These are called metastatic brain tumors, or brain metastases, and they are more common than primary brain tumors.

Brain and spinal cord tumors are named based on the type of cell they formed in and where the tumor first formed in the CNS. The following types of primary tumors can form in the brain or spinal cord:

• Astrocytic Tumors: An astrocytic tumor, or an astrocytoma, begins in star-shaped brain cells called astrocytes, which help keep nerve cells healthy.
• Oligodendroglial Tumors: This type of tumor begins in brain cells called oligodendrocytes, which also help keep nerve cells healthy.
• Mixed Gliomas: A mixed glioma is a brain tumor that has two types of tumor cells in it — oligodendrocytes and astrocytes.
• Ependymal Tumors: This type of tumor typically begins in cells that line the fluid-filled space in the brain and around the spinal cord.
• Medulloblastomas: A medulloblastoma is a type of embryonal tumor—a mass of rapidly growing cells that begins in embryonic, or fetal, tissue.
• Pineal Parenchymal Tumors: This type of tumor forms in parenchymal cells, or pineocytes, which are the cells that make up most of the pineal gland—a tiny endocrine gland in the middle of the brain that helps regulate the body’s circadian rhythm by secreting melatonin.
• Meningeal Tumors: A meningeal tumor, also known as a meningioma, forms in the meninges — thin layers of tissue that cover the brain and spinal cord.
• Germ Cell Tumors: This type of tumor forms in germ cells, which are the cells that develop into sperm in men or ova in women.
• Craniopharyngioma: A craniopharyngioma is a rare tumor that typically forms in the center of the brain just above the pituitary gland — a pea-sized organ at the bottom of the brain that controls other glands.

While the origin of most CNS tumors remains unclear, a small number of risk factors have been identified. A risk factor is anything that increases a person's chance of getting a disease. Risk factors for brain and spinal cord tumors include environmental exposures, viral infections, immunodeficiency and specific inherited syndromes. The following conditions may increase the risk of certain types of brain tumors:

• Exposure to vinyl chloride may increase the risk of glioma.
• Infection with the Epstein-Barr virus, having AIDS or receiving an organ transplant may increase the risk of primary CNS lymphoma.
• Certain genetic syndromes may increase the risk of brain tumors:
  • Neurofibromatosis type 1 or 2.
  • von Hippel-Lindau disease.
  • Tuberous sclerosis.
  • Li-Fraumeni syndrome.
  • Turcot syndrome type 1 or 2.
  • Nevoid basal cell carcinoma syndrome.

Although not all brain and spinal cord tumors can be linked to the known risk factors, advances in molecular biology and genetics are helping researchers uncover how these tumors form and progress. By studying tumor genetics, cell signaling pathways and the tumor microenvironment, scientists are identifying new markers that may predict tumor behavior and response to treatment. These discoveries are paving the way for more precise, targeted therapies and a new era of personalized care in brain cancer treatment.

“It is truly an exciting time for brain cancer research,” expressed Jonathan A. Forbes, MD, associate member of the Cancer Center and associate professor at the University of Cincinnati College of Medicine. “The field is rapidly advancing in its understanding of brain tumor biology. In August 2024, the FDA approved Voranigo, an oral medication targeting low-grade gliomas with IDH1 or IDH2 mutations. This marked the first FDA-approved systemic therapy for grade 2 astrocytomas and oligodendrogliomas in approximately two decades.” 

Jonathan A. Forbes, MD Associate Member, Cancer Prevention, Control & Population Sciences Research Program University of Cincinnati Cancer Center Program Director, Neurosurgery Residency Associate Professor, Department of Neurosurgery University of Cincinnati College of Medicine

Vorasidenib (Voranigo^®), a tablet taken by mouth, is an isocitrate dehydrogenase (IDH) inhibitor, specifically targeting the mutant IDH1 and IDH2 enzymes. This means that it blocks the activity of abnormal IDH1 and IDH2 proteins in cancer cells while largely sparing healthy cells. Unlike other IDH inhibitors, though, vorasidenib can penetrate the blood-brain barrier.

The blood-brain barrier is a network of blood vessels and tissue that is made up of closely spaced cells and helps keep harmful substances from reaching the brain. The blood-brain barrier serves as a protective shield, allowing essential substances — oxygen, water and some medications — to pass through, while preventing potentially harmful agents. However, by restricting the entry of potentially harmful substances, the blood-brain barrier often blocks many chemotherapy drugs from entering the brain.

“Until recently, neuro-oncology has been limited by the blood brain barrier, which restricts passage of molecules greater than 400 Daltons,” Forbes explained. “Recent advances in navigated focused ultrasound will help surmount this physiologic restriction and hopefully open the door to novel medications that have been effective in other forms of cancer. My colleagues and I are currently in the early stages of planning a trial to use navigated focused ultrasound to open the blood-brain barrier with combination immunotherapy for recurrent glioblastoma.”

Glioblastoma, also referred to as glioblastoma multiforme, is a grade IV astrocytoma that forms from glial tissue of the brain and spinal cord. This is a highly aggressive type of brain tumor that is characterized by rapid growth and frequent invasion of surrounding brain tissue, and it is the most common primary brain cancer in adults.

One of the challenges in treating glioblastoma is that it often escapes detection by the immune system. This is due to factors such as a low number of immune cells in the tumor — tumor-infiltrating lymphocytes (TILs) — a tumor environment that suppresses immune responses, and a low number of genetic changes that might otherwise help the immune system recognize the tumor.

To address these challenges, researchers, like Forbes, are beginning to explore combination immunotherapy. Combination immunotherapy involves using multiple immunotherapy agents or combining immunotherapy with other cancer treatments, such as chemotherapy or radiation. This approach shows promise in treating glioblastoma as it aims to overcome the challenges of glioblastoma’s unique immunosuppressive environment and enhance the immune system’s ability to target and eliminate tumor cells.

“We have also recently published some of our clinical experiences with utilizing immunotherapy for a rare type of intracranial malignancy called pituitary cancer,” Forbes shared. “Using a novel combination of immunotherapy medications in a clinical trial, we were able to achieve a complete response to therapy—with durable cure of the cancer. We are looking at investigative ways to apply this groundbreaking treatment to other malignancies of the brain and central nervous system.”

These results reflect not only the promise of immunotherapy in treating rare and aggressive brain tumors but also the strength of the collaborative research environment at the Cancer Center. At the heart of this progress is a team-based approach that brings together experts from multiple disciplines to accelerate discovery and improve patient outcomes.

“At the Cancer Center, we are incredibly privileged to have immediate and coordinated access to a number of colleagues — including basic scientists, medical and radiation oncologists — who are contributing to cutting-edge breakthroughs in cancer care on a global scale,” Forbes said. “Furthermore, I am confident that our researchers will continue the outstanding work that has differentiated our cancer care in the region.”