A Preclinical Screening Program to Identify New Brain Cancer Treatments

Darell Bigner, MD, PhD

Director, The Preston Robert Tisch Brain Tumor Center at Duke
Duke Cancer Institute

Title: Preclinical Screening Program
Investigator:  Darrell Bigner
Grantee: Duke University

Developing targeted drugs to fight brain cancer is a lengthy and expensive process.  Because brain cancer is less common than other cancers, however, most pharmaceutical companies will not invest the tremendous financial resources needed to test anticancer drugs against brain tumors.  This financial barrier slows the search for brain cancer treatments, leading to intolerable delays in identifying treatments for the very patients who need them most.

In 2002, therefore, ABC2 established the Preclinical Screening Program to solve this problem by “buying down” the risk of testing anticancer drugs in brain cancer.  Run by Dr. Darrell Bigner at Duke University, the Preclinical Screening Program allows researchers from any venue – academia, corporations, or even government agencies – to submit drugs for immediate, free-of-charge testing in animal models of malignant glioma.  By removing the financial impediment to testing new anticancer drugs, the Preclinical Screening Program fills a tremendous void in the brain cancer drug discovery and development arena and unites the biotech, pharmaceutical, and academic communities in the search for a cure.

Drugs entering the Preclinical Screening Program undergo rigorous testing in Duke’s laboratory models of malignant glioma.  These models, which consist of mice growing human brain tumors from different patients, retain characteristics of human brain cancer important for predicting a drug’s efficacy in the clinic.  During screening, the drugs undergo two rounds of testing in these models: one against tumors implanted in the body to determine preliminary efficacy, and one against tumors implanted in the brain itself to determine if a drug can enter the brain and fight cancer there.

Since its inception, the Preclinical Screening Program has made valuable contributions altering the landscape of the brain cancer therapy.  Of the several hundred drugs tested in the program, scores have shown preclinical efficacy against malignant glioma with no significant toxicity.  On the basis of this efficacy, many of these drugs advanced into clinical trials for patients with brain tumors – and one, Avastin, obtained FDA approval for use in human brain cancer.  Additionally, the screening results revealed several key concepts – for example, that combination therapies are generally much more effective than singly targeted therapies or that specific drugs can make tumors more sensitive to radiation – that will inform and improve future brain cancer treatment strategies.  Based on the success of the ABC2-initiated Preclinical Screening Program, the Preston Robert Tisch family has given additional support allowing the program to continue.

By rapidly moving potentially life-saving drugs from the laboratory to the clinic, the Preclinical Screening Program has taken meaningful steps toward identifying a cure for brain cancer.