Brain cancer takes a variety of forms – and research to better understand and treat it is progressing on a variety of fronts.
One area of focus is the tumor microenvironment the skein of tissues and blood vessels that feed and support a tumor. Researchers are exploring how newly formed brain tumors interact with surrounding cells to turn those cells into aiders and abetters of tumor growth. They’re particularly interested in how brain tumors tap into the body’s blood supply to draw in nutrients. Understanding these processes is a critical first step to devising therapies that prevent tumors from exploiting nearby tissue for their own purposes.
Work is also underway to get a better understanding of the genomic landscape of brain cancer – the set of mutations and other derangements of the genetic code that set normal brain cells on a course for cancer. Mutations found to be drivers of brain tumor cell growth are often prime targets for new drugs.
At Dana-Farber, for example, researchers recently identified several molecular alterations that drive high-grade astrocytomas, rare and fatal childhood brain cancers. At least two of the new mutations might be susceptible to blocking by existing drugs, and the others provide new opportunities for future drug development. (This whitepaper dives deeper into the science behind pediatric brain tumor research.)
Another group of Dana-Farber researchers recently identified a protein vital to both the normal development of the brain and, in many cases, of medulloblastoma, a fast-growing brain tumor that arises most often in children. When researchers cut the level of the protein called Eya1 in half in mice prone to develop a form of medulloblastoma, the animals’ risk of dying from the disease dropped sharply.
Such research into the basic mechanics of cancer often provides clues to new therapies. A discovery by Dana-Farber scientists, for example, revealed how a protein named netrin-1 helps neurons in the developing brain make connections with one another. The finding may have important applications for treating brain cancer because many cancer cells produce netrin to attract blood vessels as a source of nourishment. Switching off that process could starve a tumor or prevent it from growing.
Technical advances are helping surgeons treat the disease more effectively. Technology known as stimulated Raman Scattering microscopy helps surgeons better distinguish cancerous from normal tissue in the brain during operations, potentially improving the safety and accuracy of such procedures.
New surgical procedures enable surgeons to treat some brain tumors near the pituitary gland by using an endoscope, a thin tube with a tiny video camera at the tip. By passing the endoscope through a small hole at the back of the nose, surgeons can operate through the nasal passages, limiting potential damage to the brain.
One of the major challenges of delivering chemotherapy agents to the brain is the blood-brain barrier, a dense web of tissue that prevents many drug molecules from reaching the brain. Investigators are testing convection-enhanced delivery, in which a small tube is placed into a brain tumor through a small hole in the skull. An infusion pump connected to the tube can send drugs directly to the tumor.
Immunotherapies, which rally the body’s immune system to fight disease, are showing promise in brain cancer. Dana-Farber investigators recently tested immunotherapy agents known as checkpoint inhibitors in mice with glioblastoma, an incurable form of brain cancer. The results were so encouraging – many of the mice were considered cured, and many had no evidence of tumor two months after treatment – that investigators have begun clinical trials of the agents in human patients.