Of the hundreds of types of cancers that can afflict the human body, brain cancer poses some of the toughest treatment challenges. Getting drugs into the brain can be difficult because a barrier physically shields the brain from chemicals circulating in the body. Medications that do enter the brain may cause serious side effects.

Memorial Sloan-Kettering Cancer Center’s new Brain Tumor Center (BTC) is working to overcome these obstacles using recently revealed insights into the molecular and cellular properties of tumors. Scientists are trying to create therapies that target cancer cells and the abnormal signaling pathways needed to maintain them.

The Simons Foundation supports this important work by underwriting preclinical studies of new therapies for the type of tumors called gliomas to confirm that they produce their desired effect in animal models. There currently exists no drug pipeline developed specifically for gliomas, and such preclinical work is an essential step in the design of new therapies for use in humans.

The BTC is undertaking both basic scientific investigations into brain tumors and translational research in which potential new targets and therapies make the transition from animal experiments to humans.

One major goal at BTC is to find chemicals that can be used in glioma treatment. In a gleaming room in Memorial Sloan-Kettering’s new research tower on Manhattan’s Upper East Side, the arms of a robotic laboratory click and whirr. Machines are testing 250,000 compounds to see if they might be useful in killing tumor cells. The screening machines have found several compounds that enhance the ability of radiation to kill cancer cells, specifically block cell proliferation, inhibit development of specific stem cells and prevent cancer cell survival.

“These machines can screen compounds thousands of times faster than we could in the past,” said Hakim Djaballah, the director of the high-throughput screening core facility.

BTC director Dr. Eric Holland has developed a promising new system for glioma modeling. Holland’s colleagues, neurosurgeon Philip Gutin and Shahin Rafii, a hematologist at Weill Cornell Medical College, are seeking to treat tumors by cutting off their blood supply. The team is studying the use of blood supply-producing cells derived from bone marrow.

Research into brain tumors may also be useful in understanding autism. Of the several candidate genes that enhance the risk for autism uncovered so far, three – PTEN, TSC1 and TSC2 – are part of biochemical pathways that suppress the formation of tumors. Disabling these genes in mice produces signs and symptoms that are relevant to autism in humans.

“Putting Memorial Sloan-Kettering’s basic science people together with neurosurgeons and medical oncologists and radiation oncologists – everyone who treats brain tumors – facilitates the exchange of ideas among investigators with conjoined interests,” said Dr. Holland.