Our laboratory has been at the forefront of investigating therapeutic interventions targeting Esophageal Adenocarcinoma (EAC), a malignancy with significant clinical challenges. Our findings on the efficacy of WEE1 inhibitors in EAC cells, both in vitro and in vivo, have been groundbreaking. This has driven us to hypothesize and explore the potential benefits of combining WEE1 inhibition with FDA-approved immune checkpoint inhibitors in the treatment of EAC.

Recent data we gathered provided promising insights into the potential of WEE1 inhibitors in attenuating tumor growth in the immune-competent EAC mouse model. In a bid to augment these findings and explore synergistic therapeutic effects, we are now investigating the concurrent use of WEE1 inhibitors and immune checkpoint inhibitors like Pembrolizumab (anti-PD-1), Atezolizumab (anti-PD-L1), and Ipilimumab (anti-CTLA-4). Employing our in-house developed EAC mouse models, especially the EAC IL-1β +/+ and EAC Wee1-cKO strains, we aim to understand the cellular and molecular predictors of therapeutic responses. Such insights are invaluable, potentially directing future clinical trials and refining therapeutic strategies for patients.

One significant challenge in treating EAC, akin to other malignancies, is the emergence of resistant cells, often leading to treatment failure and disease resurgence. Hence, our investigations also encompass understanding the cellular and molecular underpinnings of this resistance, particularly focusing on immune cell responses after WEE1 inhibition. By leveraging advanced techniques like IHC, Mass cytometry, and CyTOF, we aim to pinpoint specific immune cell populations that are most responsive to WEE1 inhibition.

Moreover, as part of our broad-spectrum research, we've been examining the potential of WEE1 conditional knockdown combined with immune checkpoint blockage to understand EAC's immunological dynamics better. Our experiments, conducted at the esteemed Division of Veterinary Resources (DVR) of the University of Miami, aim to delve deeper into the rate of tumor formation, tumor size variations among different groups, tumor immune cell infiltration changes, and immune checkpoint molecule expression. These metrics provide a comprehensive understanding of the therapeutic efficacy of our proposed interventions.

In conclusion, our laboratory remains steadfast in our commitment to push the boundaries of EAC research. We believe that our rigorous investigations, coupled with our innovative approaches, will pave the way for more effective, personalized treatments for those afflicted with EAC.