"Becoming the recipient of the highly regarded Sontag award will place me in a network of of highly dedicated clinicans and scientists who are single-mindedly dedicated to the cure of malignant gliomas."
- Dr. Clark Chen
- Associate Professor, University of California, San Diego
About DSA-Funded Research
Much of glioblastoma therapeutic efforts have been focused on direct inhibition of oncogenes or genes modulating the tumor microenvironment. However, there is genetic evidence suggesting a broader class of therapeutic targets. It has long been observed in yeast and other genetic models that certain combinations of mutations result in cell death, when each mutation alone fails to produce such an effect. This phenomenon is known as synthetic lethality. It is thought that the first mutation introduces cellular stress that forces the cell to depend on compensatory processes that are then inactivated by the second mutation. The principle of synthetic lethality should be applicable to oncogenes since they are fundamentally mutated genes. The implication is that the tumor state depends on the activities of a wide variety of compensatory pathways that are not directly related to the oncogene itself. One study in yeast identified an average of six synthetic lethal combinations per mutation, suggesting that there are at least six distinct ways to kill cancer cells beyond direct oncogenic inhibition. The funding provided by the Sontag Foundation affords an opportunity to explore this paradigm as means for glioblastoma therapeutic development.
"Clark's ability to focus and tenaciously pursue new knowledge for his own benefit and the benefit of others is impressive."
Bob S. Carter, M.D., Ph.D.
University of California, San Diego Medical School
"While clearly excelling as a neurosurgeon-in-training in the clinical setting, Clark maintained his burning interest in applying his basic science training to the development of glioblastoma therapy."
Alan D. D'Andrea, M.D.
Dana-Farber Cancer Institute
- Lionel ML Chow “Differential localization of glioblastoma subtype: implications on glioblastoma pathogenesis"
- Li J, Zhu S, Kozono D, Ng K, Futalan D, Shen Y, Kushwaha D, Schlabach M, Carter BS, Kwon C, Furnari F, Cavenee W, Elledge S, Chen CC. Genome-wide shRNA screen revealed integrated mitogenic signaling between Dopamine Receptor D2 (DRD2) and Epidermal Growth Factor Receptor (EGFR) in glioblastoma. Oncotarget 2014; 5(4): 882-93.
- Shen Y, Li J, Nitta M, Futalana D, Steed T, Treiber JM, Taich Z, Stevense D, Wykoskye J, Chen H, Carter BS, Becher OJ, Kennedy R, Esashih F, Sarkaria JN, Furanri FB, Cavenee WK, Desai A, Chen CC. Orthogonal targeting of EGFRvIII expressing glioblastomas through simultaneous EGFR and
PLK1 inhibition. Oncotarget, 2015; 6(14): 11751-67.
- Steed TC, Treiber JM, Patel K, Ramakrishnan V, Merk A, Smith AR, Carter BS, Anders M Dale AM, Chow LML, Chen CC. Differential localization of glioblastoma subtype: implications on glioblastoma pathogenesis. Oncotarget 2016, Epub.
- Kozono D, Li J, Nitta M, Sampetreanc O, Gonda D, Kushwahaa DS, Merzona D, Ramakrishnan V, Zhu S, Zhua K, Matsui H, Harismendy O, Hua W, Mao Y, Kwon C, Saya H, Nakano I, Pizzo DP, VandenBerg SR, Chen CC. Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression. Proc. Natl. Acad. Sci. U.S.A. 2015; 112(30): E4055-64.