Our lab is focused on developing new therapies for pediatric
sarcomas. Many of these tumors are driven by oncogenic
transcription factors generated by reciprocal chromosomal
translocations. These mutations are responsible for the continued
proliferation of these tumors and occur in a genetic background
characterized by a limited number of cooperating somatic mutations.
Unfortunately, these fusion proteins are transcription factors and
therefore represent challenging small molecule drug targets. Our
work is focused on developing methods and compounds to target these
specific transcription factors. To date, we have primarily worked
to identify compounds that inhibit the dominant oncogene of Ewing
sarcoma, the EWS-FLI1 transcription factor. We have completed a
high throughput screen to identify mithramycin as an inhibitor of
EWS-FLI1. We have translated this compound to the clinic in a phase
I/II trial currently accruing patients at the National Cancer
Institute. In addition, we have utilized clinical observations to
identify trabectedin as an inhibitor of EWS-FLI1. We are now
working to improve the activity of both compounds by studying novel
analogs and developing novel mechanism-based combination therapies.
We are studying the mechanism of action of these and other
compounds known to interfere with specific transcription factors.
Finally, we are working to understand the most effective way to
utilize small molecules to poison specific transcription factors.
The following timeline graph is generated from all co-authored publications.
Featured publications are shown below:
- A Decade in Banking Ewing Sarcoma: A Report from the Children's Oncology Group. Borinstein SC, Beeler N, Block JJ, Gorlick R, Grohar P, Jedlicka P, Krailo M, Morris C, Phillips S, Siegal GP, Lawlor ER, Lessnick SL, COG Ewing Sarcoma Biology Committee (2013) Front Oncol : 57
› Primary publication · 23519678 (PubMed) · PMC3602933 (PubMed Central)
- Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Wan X, Harkavy B, Shen N, Grohar P, Helman LJ (2007) Oncogene 26(13): 1932-40
› Primary publication · 17001314 (PubMed)