Benjamin W. Purow
Associate Professor of Neurology and
Biochemistry & Molecular Genetics
M.D. Johns Hopkins
New therapeutic approaches to glioblastoma and other cancers

 

The Purow laboratory is dedicated to developing innovative approaches to treating brain tumors and other cancers. We are focused on the following areas:

  • We have shown that a pathway important in stem cells, called the Notch pathway, is a potential target for gliomas, the most common and lethal brain tumors. We have further demonstrated that a class of drugs in clinical trials for other functions also acts to inhibit Notch.

  • microRNAs are small RNA molecules that are found throughout our DNA but that are not used to generate proteins. They do, however, play powerful roles in regulating expression of genes that do code for proteins, and have been found to be important in almost every area in biology-including cancer. We have found a number of microRNAs that can promote or suppress survival in glioblastoma, the most aggressive gliomas. Delivery of tumor-suppressive microRNAs is showing potential to treat brain tumors in our mouse models, and we hope to eventually move these studies forward to clinical trials.

  • In a project arising from our microRNA work, we have shown that a protein called DGKalpha is a promising cancer target in brain cancers but also in other cancers as well. Our first paper on this was recently published in Cancer Discovery. DGKalpha inhibition appears to have exciting potential to boost the effects of other anti-cancer therapies, such as radiation and possibly immunotherapy as well. Chemical blockers of this protein already exist, and we have identified a nearly identical compound that has already been found safe in clinical trials in people as a psychiatric medication. We have confirmed that this compound also functions as a DGKalpha inhibitor, potentially allowing this strategy to proceed rapidly to clinical trials in patients.

  • In the same vein of repurposing old drugs, we are also investigating anti-cancer functions of medications approved for other indications. These studies could allow rapid translation to patients in the clinic. In one such project in the early stages, we have followed leads from the recently-released online database CellMiner to show that a widely-used class of medications effectively inhibits the TGF-beta signaling pathway, and appears particularly toxic to cancer cells with a more mesenchymal phenotype.

  • We are seeking to further leverage the CellMiner database to identify compounds with possible synthetic lethal activity against cancer cells with difficult-to-target lesions in tumor suppressor genes. At present in our lab and with a collaborator we are initiating studies to test two of these leads.


Selected References

Guessous F, Alvarado-Velez M, Marcinkiewicz L, Zhang Y, Kim J, Heister S, KefasB, Godlewski J, Schiff D, Purow B, Abounader R. (2013) "Oncogenic effects of miR-10b in glioblastoma stem cells." J Neurooncol. 112:153-63. doi: 10.1007/s11060-013-1047-0. Epub 2013Jan 10. [PubMed]

Floyd DH, Kefas B, Seleverstov O, Mykhaylyk O, Dominguez C, Comeau L, Plank C,Purow B. (2012) "Alpha-secretase inhibition reduces human glioblastoma stem cell growth in vitro and in vivo by inhibiting Notch." Neuro Oncol. 14(10):1215-26. Epub 2012 Sep 7. [PubMed]

Sun J, Gong X, Purow B, Zhao Z. (2012) "Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma." PLoS Comput Biol. 8:e1002488. doi: 10.1371/journal.pcbi.1002488. Epub2012 Jul 19. [PubMed]

Jo J, Schiff D, Purow B. (2012) "Angiogenic inhibition in high-grade gliomas: past, present and future." Expert Rev Neurother. 12:733-47. doi: 10.1586/ern.12.53. [PubMed]

Purow B. (2012) "Notch inhibition as a promising new approach to cancer therapy." Adv Exp Med Biol. 727:305-19. doi: 10.1007/978-1-4614-0899-4_23. [PubMed]

Duex JE, Comeau L, Sorkin A, Purow B, Kefas B. (2011) "Usp18 regulates epidermal growth factor (EGF) receptor expression and cancer cell survival via microRNA-7." J Biol Chem. Jul 286(28):25377-86. doi: 10.1074/jbc.M111.222760. Epub2011 May 18. [PubMed]