Can an acne drug effectively treat low-grade gliomas?

Overview:  We are funding the development of a clinical trial to determine if retinoic acid -- Accutane – might be an effective brain cancer treatment for patients with IDH mutations. 

Challenge:  The idea to use retinoic acid as an anti-cancer therapy is not new.  During the early 1990s dozens of brain tumor patients were treated with Accutane, but most patients in the study did not experience a significant improvement in overall survival.  While the story of this skin medication trying to kill cancer might have ended there, the original clinical trials were conducted before cancer researchers were able to perform genomic profiling of tumor tissue.  As a standard practice, the UCLA Neuro-Oncology group is in the process of retrospectively profiling every tumor tissue sample in their bio-bank.  During this review an interesting finding emerged, buried in their extensive data set. 

The initial analysis showed that patients with IDH1 mutations treated with Accutane lived a median of 81 months, while those patients not treated with the drug lived only 36 months; more than doubling a patient’s life expectancy.

Opportunity:  While there are dozens of clinical trials seeking to develop drugs to treat glioblastoma, there aren’t any viable drug candidates in the clinic specifically designed to treat low grade gliomas, the majority of which have IDH mutations.  Accutane is an appealing and exciting drug candidate since it is already approved by the FDA, is relatively safe, and is available as an inexpensive generic. 

Clinical Study:  The UCLA team hypothesizes that IDH1 mutant gliomas have deficient retinoic acid metabolism and can be effectively treated with synthetic retinoic acid.  The primary purpose of this clinical study is to evaluate whether retinoic acid (Accutane) in combination with standard radiation and chemotherapy is an effective treatment for patients with IDH1 mutant gliomas.

The Clinical Study has three specific aims:

1)  Validate the initial UCLA findings by collecting additional IDH mutated tumor tissue samples from patients treated with Accutane.  UCSF, MD Anderson, and the German Glioma Network are all centers with significant bio-repositories.

2)  Determine pharmacodynamic (PD) markers to be able to assess whether Accutane is affecting the intended target.

3)  Initiate a multi-arm Accutane clinical study, which will include about 200 glioma patients.

Our Team:  Linda Liau, Tim Cloughesy, and Albert Lai; Neuro-Oncology & Neurosurgery, UCLA; Don Lo, Director, Duke Center for Drug Discovery



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