Anna Joy, PhD
Glioblastoma is the most common primary brain tumor. Because complete surgical removal is problematic and the remaining tumor cells are very resistant to chemotherapy and radiation, new treatment options are urgently needed for these patients.
Presently, glioblastomas are diagnosed based on microscopic appearance treated as though they are one disease. However, we now know these tumors are a collection of molecular subtypes. Emerging evidence suggests subtypes can take different molecular pathways to tumorigenicity.
Not accounting for these subtypes impedes drug development on many levels. Patients with different drug sensitivities and natural courses confound clinical trials, increasing their cost and limiting the number of new drugs that can be tested. Investigating all glioblastomas without regard to their subtype also obfuscates new therapeutic targets and drugs that work well only on specific tumor subtypes.
Unfortunately, molecular classification of glioblastoma is in a nascent stage, and cannot be used reliably for patient treatment and drug development. We have developed a robust classification system for glioblastoma based on the growth-promoting, cancer-driving PI3K/AKT pathway. Using this system, we have identified five subtypes of glioblastoma, each with unique underlying molecular aberrations and aggressiveness.
Through close study of each subtype, we were able to find new drug targets that could not be found by studying glioblastomas as a whole. Importantly, we found evidence that an approved chemotherapy drug significantly extends survival of patients with a specific tumor subtype. This suggests AKT classification can be used as a biomarker to select appropriate therapies for glioblastoma patients.
A major goal of our laboratory is to refine this classification method, develop models of each subtype, and use them to find and test new therapeutic agents. We plan to develop AKT classification as a biomarker for use in optimizing clinical trial design and translating subtype-specific therapeutic targets into new treatments for glioblastoma patients. We ultimately hope this work will help guide individualized treatments for glioblastoma patients.
We are also working on a second project to investigate how to therapeutically target the growth-promoting, cancer-causing PI3K/AKT pathway. Pathway inhibitors have antitumor activity in other cancers, but they have failed clinical trials in glioblastoma.
We are combining AKT classification with molecular studies of important pathway proteins to find which pathway component to target and how each subtype is resistant to pathway inhibitors. We hope to translate this research into new effective drugs that shut down the pathway and extend survival of glioblastoma patients without sacrificing quality of life.
We do not have any open positions at this time, but please contact us for information about volunteering in the laboratory and graduate or undergraduate research.
Anna Joy, PhD
Laboratory of Basic and Translational Neurooncology Research
Office: (602) 406-8356