Brain Cancer

By understanding the molecular features of brain tumors, LSP researchers aim to develop novel targeted approaches for treating refractory diseases. 

The standard-of-care for managing brain tumors is surgical resection, followed by chemotherapy and/or radiation for higher-grade tumors. While adjuvant chemotherapies reduce the risk of recurrence, limit disease progression, and maximize survival, they may be associated with significant detrimental effects. In part, this is because treatment approaches also damage healthy cells: systemic chemotherapy may lead to a weakened immune system and hair loss, while localized radiotherapy may lead to long-term consequences such as increased risk of stroke. Targeted therapies provide an alternative treatment approach, directing drugs to tumor cells while leaving non-tumor cells unharmed.

Research at the LSP led by physician-scientist and neuropathologist Sandro Santagata aims to identify molecular features of brain tumors that can inform targeted therapeutic approaches. Dr. Santagata’s early pivotal work identified that nearly all papillary craniopharyngiomas (a rare type of brain tumor) share a recurrent activating mutation in the proto-oncogene BRAF, which is altered in a wide variety of cancers. Targeting this specific BRAF mutation (p.V600E) in papillary craniopharyngioma patients can dramatically reduce tumor volume [i], with 15/16 patients (94%) responding to combination BRAF-MEK inhibition in a successful Phase II clinical trial [ii]. 

Dr. Santagata’s current research uses computational pathology and multimodal tissue profiling to identify unique features of the brain tumor microenvironment. These insights inform the development of new strategies for treating cancer, including antibody-drug conjugates [iii], immune checkpoint (PD-1/PD-L1) inhibitors [iv], and modulators of CD73 and immunomodulatory purinergic signaling [v], leading to additional ongoing clinical trials [NCT05465174]. Our research spans many types of rare brain tumors, including glioblastoma, pediatric glioma, meningioma, ependymoma, craniopharyngioma, and others.