Breelyn Wilky, M.D.
Assistant Professor of Medicine
Description of Research
The identification of molecular targets for drug development in sarcomas has been challenging in past years, due to the rarity, heterogeneity, and genetic complexity of the tumors. By helping to expand primary human sarcoma tissue banking and facilitating increased genomic and cellular pathway profiling, Dr. Wilky aims to translate basic science observations to novel clinical studies. During her prior research years at Johns Hopkins in the laboratory of David Loeb, MD, PhD, Dr. Wilky studied the cytotoxic effects of targeted agents in several preclinical sarcoma models. She identified that RNA helicase DDX3 was highly expressed in a variety of human sarcomas, and that inhibition of DDX3 function by RNA inhibition markedly impaired Ewing’s sarcoma cell growth and tumor formation. Additionally, treatment with RK-33, a novel small molecule DDX3 inhibitor, resulted in promising cytotoxic activity in mouse sarcoma xenografts. The drug is now undergoing required studies for investigative new drug status, and Dr. Wilky’s current focus is to design the initial first-in-human phase I study of RK-33, enriched with sarcoma patients. By collaborating with basic researchers at the University of Miami and working to better understand genetic and molecular mechanisms in sarcomas, she hopes to identify other targets to expand therapeutic options for sarcoma patients outside of standard chemotherapies.
- Performed true bench-to-bedside studies of RNA helicase DDX3 in sarcomas, which may potentially support further development of an entirely new class of antineoplastic therapy, helicase inhibitors
- Prior experience in design and analysis of phase I and phase II clinical trials, with interest in adaptive design methodology and development of informative correlative studies
- Compiled a large retrospective study of solitary fibrous tumors at Johns Hopkins, reporting novel prognostic features that may help to predict patients likely to recur after resection
- Significant experience in preclinical drug development methods and study design, well-acquainted with practical and logistic aspects of managing tissue banking and resulting databases
Selected Cancer-Related Publications
- Trucco MM, Awad O, Wilky BA, Goldstein SD, Huang R, Walker RL, Shah P, Katuri V, Gul N, Zhu YJ, McCarthy EF, Paz-Priel I, Meltzer PS, Austin CP, Xia M, Loeb DM. A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-?B Signaling in Chordoma Biology. PLoS One 8:e79950,2013 Read more »
- Wilky BA, Meyer CF, Trent JC. Pazopanib in sarcomas: expanding the PALETTE. Curr Opin Oncol 25:373-8,2013 Read more »
- Wilky BA, Montgomery EA, Guzzetta AA, Ahuja N, Meyer CF. Extrathoracic Location and Borderline Histology are Associated with Recurrence of Solitary Fibrous Tumors After Surgical Resection. Ann Surg Oncol 20:4080-9,2013 Read more »
Collaborating in the Multidisciplinary Research Program(s):