Why did I get this brain tumor?

Fall 2017

italy

Liz is a very active schoolteacher, mother, wife and athlete, lives with a glioma, the most common type of brain cancer in adults. She has been a patient in the UCLA Neuro-Oncology program in the Department of Neurology for the past 11 years.  She has endured brain surgery, radiation, and chemotherapy and now comes in to clinic for surveillance magnetic resonance imaging (MRI) scans every 6 months.  She was 39 years old when she was diagnosed after seizures.  During this time, she has been able to raise three wonderful kids, and travel all over the world (see recent picture from Montepulciano, Italy).  Like other patients, she asked at one of her initial visits: “Why did I get this brain tumor?”   The answer includes recent developments in our understanding of the molecules and mutations in brain tumors that have come out of UCLA Neurology labs. For the past 15 years, Dr. Albert Lai, Associate Professor in Residence, has worked tirelessly with colleagues at UCLA to improve outcomes for patient with gliomas, the most common brain cancer in adults.  As a neuro-oncologist who has seen hundreds of patients over his career, Dr. Lai, like his colleagues, wondered why the gliomas diagnosed in younger adults like Liz were different than those diagnosed in older adults.  These differences include how they look on MRI scans and how they respond to treatment.  In 2008, an abnormally mutated gene was discovered in the gliomas of younger adults that was not present in those of the older adults.  This gene encodes for Isocitrate Dehydrogenase (IDH), a crucial metabolic enzyme. Soon after the initial discovery in gliomas, these mutations have also been found in other malignancies.   Since 2008, rapid advances in understanding the basic elements of this disease pathway have been made, enabling the development of specific oral inhibitors for IDH mutations in leukemias which received FDA approval this year.

Much work remains to effectively target this pathway for patients diagnosed with gliomas.  Critical to this endeavor will be a continued focus on understanding how this mutation arises in younger adult glioma patients and how it generates a distinct phenotype.  Since 2013, with funding from the National Institute of Health National Cancer Institute, Dr. Lai’s laboratory has been trying to elucidate the basic mechanisms in which the IDH mutation contributes to glioma formation.   Specifically, Dr. Lai has been focused on unraveling the connection between the IDH mutation and changes in the way that brain cells regulate their genome, termed “epigenetic changes.”  This strategy has led to identification of novel pathways of communication with these cells that may one day represent therapeutic targets.

In recognition of Dr. Lai’s work and the world-class performance of integrated brain cancer research at the university, UCLA has recently been designated as a Specialized Program of Research Excellence, or SPORE, by the National Cancer Institute, making it one of only five brain cancer programs nationwide to receive this national recognition and its accompanying substantial research funding.

Dr. Lai serves as a co-leader with Dr. Harley Kornblum as the Basic Science co-leader on the project entitled, “Novel epigenetic treatment of IDH mutant gliomas.”  In a clinical area that has only seen modest improvements in outcomes over the years, Dr. Lai’s efforts, in concert with larger efforts at UCLA, will help advance research and contribute to improved treatments for these glioma patients.  Dr. Lai has been excited to contribute to an example of how molecular alterations in critical pathways can be identified in patients, understood in the laboratory, and successfully targeted at the bedside.  Soon, he hopes to be able to tell a patient why they developed a brain tumor and how it can be cured.

Join the conversation…Dr. Lai will answer questions about this piece and his work in Neuro-Oncology on Twitter, Wednesday December 13th, 9-4pm (Pacific Time) @UCLANeurology. Please note: Dr. Lai can not answer patient-specific questions.