Open Access Highly Accessed Open Badges Research

Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs

Pengfei Jiang1, Rajesh Mukthavavam1, Ying Chao1, Ila Sri Bharati1, Valentina Fogal1, Sandra Pastorino1, Xiuli Cong3, Natsuko Nomura1, Matt Gallagher1, Taher Abbasi4, Shireen Vali4, Sandeep C Pingle1, Milan Makale1 and Santosh Kesari123*

Author Affiliations

1 Translational Neuro-Oncology Laboratories, Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA

2 Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA

3 Moores Cancer Center, UC San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093, USA

4 CellWorks Inc., Irvine, CA USA

For all author emails, please log on.

Journal of Translational Medicine 2014, 12:13  doi:10.1186/1479-5876-12-13

Published: 17 January 2014



Glioblastoma (GBM) is a therapeutic challenge, associated with high mortality. More effective GBM therapeutic options are urgently needed. Hence, we screened a large multi-class drug panel comprising the NIH clinical collection (NCC) that includes 446 FDA-approved drugs, with the goal of identifying new GBM therapeutics for rapid entry into clinical trials for GBM.


Screens using human GBM cell lines revealed 22 drugs with potent anti-GBM activity, including serotonergic blockers, cholesterol-lowering agents (statins), antineoplastics, anti-infective, anti-inflammatories, and hormonal modulators. We tested the 8 most potent drugs using patient-derived GBM cancer stem cell-like lines. Notably, the statins were active in vitro; they inhibited GBM cell proliferation and induced cellular autophagy. Moreover, the statins enhanced, by 40-70 fold, the pro-apoptotic activity of irinotecan, a topoisomerase 1 inhibitor currently used to treat a variety of cancers including GBM. Our data suggest that the mechanism of action of statins was prevention of multi-drug resistance protein MDR-1 glycosylation. This drug combination was synergistic in inhibiting tumor growth in vivo. Compared to animals treated with high dose irinotecan, the drug combination showed significantly less toxicity.


Our data identifies a novel combination from among FDA-approved drugs. In addition, this combination is safer and well tolerated compared to single agent irinotecan.


Our study newly identifies several FDA-approved compounds that may potentially be useful in GBM treatment. Our findings provide the basis for the rational combination of statins and topoisomerase inhibitors in GBM.

Glioblastoma; Drug screening; Patient-derived glioblastoma cell lines; Rational combination