Graduate students Dalia Tarek Fleifel (Cook lab) and Humeyra Kaanoglu (Sancar Lab) presented their research posters at聽the聽American Association for Cancer Research (AACR) annual meeting in Chicago during the week of聽April 25-30, 2025.
Dalia Fleifel, PhD Candidate in the Cook lab
Abstract title is: 鈥淯nraveling c-MYC role in DNA replication origin licensing through non-canonical pathways鈥�
MYC is a frequently dysregulated oncogene in >70% of cancers where its overexpression drives aberrant cell cycle progression and increased proliferation: a common feature of aggressive cancers. At the AACR 2025 meeting, multiple parallel attempts to inhibit or degrade MYC were discussed by industry leaders. However, MYC is hard to target due to its intrinsically disordered structure and essential functions in normal cells. Therefore, finding clever ways to target it or better, targeting downstream effectors is of urgent need. Moreover, understanding the mechanisms by which MYC drives aberrant cell cycle progression is crucial. In a poster presentation, Dalia shared with the AACR community her work identifying non-canonical pathways by which MYC drives rapid DNA replication origin licensing – a rate-limiting step of cellular proliferation. Importantly, Dalia identified key effectors in the downstream MYC pathways that could be targeted and exploited in MYC-driven cancers.
Humeyra Kaanoglu, PhD Candidate in the Sancar Lab
Abstract title is: “Repurposing the DNA Labeling Agent EdU for Therapy Against Heterogeneous Patient Glioblastoma”
In this study, we repurpose the DNA labeling agent 5-ethynyl-2鈥檇eoxyuridine (EdU)as a treatment for GBM. We tested the efficacy of EdU in several different model systems, including (i) GBM cell lines in in vitro cell culture, (ii) in vivo orthotopic mouse models of GBM, and (iii) against living, uncultured GBM patient tumor tissues grown within our Organotypic Brain Slice Culture (OBSC) ex vivo platform. When compared to the standard of care drug TMZ in in vitro GBM cell survival assays, EdU displayed ED50 (effective dose killing 50% of cell population) values orders of magnitude lower than TMZ in all four GBM tumor lines tested. Against two in vivo orthotopic brain tumor models, EdU significantly extended survival relative to controls. EdU efficacy against a panel of patient GBMs largely correlated with the clinical Ki-67 status (i.e. tumor aggressiveness) of each tumor, except one tumor that remained unresponsive to treatment with both EdU and TMZ. In conclusion, we demonstrated that EdU has potential to be repurposed as an anticancer therapeutic with survival benefits in vivo and is especially adept at killing rapidly proliferating cells with low off-target toxicity. Currently, we are focusing on further validation of EdU鈥檚 efficacy in glioblastoma treatment using different mouse models. 聽Our ultimate goal is to advance this compound into clinical trials for glioblastoma patients.