Precision Medicine

“Precision medicine” — sometimes referred to as “individualized medicine,” “personalized medicine,” or “targeted therapy” — is, in basic terms, matching the right patients, to the right medicines, at the right time. This means gaining a deeper understanding of the specific biological, genetic, and/or molecular characteristics that are driving a patient’s tumor growth and finding or developing drugs to target those particular molecular abnormalities that are responsible for the disease.

Current Funded Research

Evaluation of ONC201 in Newly Diagnosed Diffuse Glioma Patients 

Lead Investigators: Chimerix 

Project Description: Funds from this grant will be used to support work related to the phase III ACTION trial of the drug ONC201 in newly diagnosed diffuse glioma patients harboring the H3 K27M mutation. The ACTION trial is a randomized, controlled, international, phase III study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether treatment with ONC201 following radiotherapy will extend overall survival and progression-free survival in this population.

Therapeutic Approaches that Target Apoptotic Blocks in Glioblastoma (GBM)

Lead Investigators: David Nathanson, PhD, Associate Professor, Molecular and Medical Pharmacology, Elizabeth Fernandez, and Dr. Timothy Cloughesy at University of California, Los Angeles (UCLA)

Project Description: This project studies why GBM tumors are highly resistant to therapy-induced cell death. The Nathanson Lab identified that GBM tumors have two molecular blocks to prevent GBM cell death. Common therapies for GBM, such as radiation and/or chemotherapy, disable one of the two blocks, leaving a sole dependency on the other for GBM cell survival. Working with a biopharmaceutical company, the team discovered that combining a new and safe clinical drug together with radiation/chemotherapy could wear down both blocks, consequently triggering GBM tumor cell death and prolonging survival in laboratory models of GBM tumors.

Investigation of Novel Therapies in Meningiomas Using Preclinical Models

Lead Investigators: Drs. Priscilla K. Brastianos, Director, Central Nervous System Metastasis Center, Mass General Cancer Center (MGH), and Associate Professor of Medicine at Harvard Medical School, and Rachael Vaubel, Neuropathologist and Assistant Professor of Laboratory Medicine and Pathology at the Mayo Clinic

Project Description: This project is currently validating a novel combination of drugs that target common mutations in meningiomas. This combination has demonstrated decreased tumor growth in laboratory models of meningioma. Pending positive results from this study, plans are in place for rapid translation of this combination into the clinic in partnership with Alliance for Clinical Trials in Oncology.  

Lipid Nanoparticles for Precision Gene Editing in Glioblastoma

Lead Investigators: Anna Krichevsky, PhD, at Brigham and Women’s Hospital

Project Description: Dr. Anna Krichevsky’s lab has shown promising laboratory results in models of GBM by targeting microRNA-10b (miR-10b), a critical regulator of glioma growth and a promising new therapeutic target for malignant gliomas, especially GBM. MicroRNAs are small, non-coding RNA molecules that regulate gene function in cells and, despite challenges with miRNA inhibitors and their delivery methods, the lab has developed a groundbreaking drug that enables gene editing of miR10-b. The gene editing of miR-10b interferes with the production of this molecule, which is essential for GBM growth. 

 Past Funded Research Highlights

NBTS has maintained an acute focus on funding precision medicine-related research over the past decade. Particularly through past NBTS initiatives like the Defeat GBM and Defeat Pediatric Brain Tumors Research Collaboratives, scientific discovery has advanced our understanding of brain tumors to an extraordinary degree, allowing never-before-seen glimpses into the secrets that tumors had been hiding for centuries. Critically, we’ve been able to identify a variety of molecular culprits that lead to uncontrolled tumor growth as well as potential ‘Achilles Heels’ that may leave certain tumors vulnerable to new, emerging treatment strategies. 

NBTS-funded research has contributed, or directly led, to the discovery of a number of the most important “biomarkers,” or tumor characteristics, that are essential for researchers and doctors to better diagnose patients, plan treatment strategies, and make sure patients can choose a tailored treatment and/or clinical trial, including:

• Discovery of the IDH (isocitrate dehydrogenase) mutation, which has become a critical means for neuro-oncologists to distinguish between different types of gliomas, and now is the basis of a new, recently approved targeted therapy for patients with grade II astrocytoma and oligodendroglioma.
  
• Discovery of the EGFR mutations, which are the most common mutations found in glioblastoma and represent key targets for which many GBM treatment strategies are being developed.
  
• Discovery of the 1p/19q co-deletion, which is the key characteristic for identifying and diagnosing low-grade gliomas, including oligodendrogliomas.
  
• Discovery of the histone 3.3 mutations, now considered the key driver of pediatric high-grade gliomas.

Informed in 30: Precision Medicine

NBTS’s Informed in 30 educational video series took a deep dive into precision medicine.