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Purpose: Prostate cancer has emerged as a significant public health challenge in the Middle East, characterized by rising incidence rates and a concerning mortality-to-incidence ratio. Yet, despite these alarming trends, data regarding prostate cancer awareness in the region remain limited. To address this critical knowledge gap, this study investigates prostate cancer awareness within the Middle East., Materials and Methods: A cross-sectional survey was performed among 5,913 men age 40 years and older across 14 Middle Eastern countries between January 1, 2022, and July 31, 2023. Excluding those with a history of prostate cancer, a validated questionnaire assessed prostate cancer awareness. Data were analyzed using frequencies and percentages for categorical variables, medians and ranges for continuous variables, and Pearson chi-square analysis for relationships between education levels and awareness of prostate cancer., Results: The survey achieved a 74.9% response rate, with 4,431 male participants. Regarding prostate cancer awareness, 83.8% of participants had heard of the disease. However, only 31.0% correctly identified it as the most common malignancy in men, and 21.8% believed it affects both sex. Awareness of screening was limited, with just 19.1% recognizing the prostate-specific antigen test's role. Additionally, participants had a pessimistic view, with a mean perception that 75% of patients with prostate cancer die from the disease, rather than from other causes. Higher education levels were associated with significantly increased awareness of prostate cancer ( P < .001)., Conclusion: This study reveals that while general awareness of the disease exists, crucial knowledge deficits regarding risk factors, screening, and prognosis are evident. Addressing these knowledge gaps through culturally tailored education may improve early detection rates, treatment outcomes, and ultimately reduce the burden of prostate cancer in the Middle East.

Head and neck squamous cell carcinomas (HNSCC) are well suited for cancer vaccination strategies. In addition to tumor-associated antigens (TAAs) and endogenous retrovirus (ERV) encoded proteins, HNSCCs have a relatively high tumor mutational burden encoding potential neoepitopes. Peptide vaccine candidates are prioritized by predicted high-affinity to major histocompatibility complex (MHC) class I with MHC-II affinity largely not being considered. Herein, we extend previous studies to evaluate therapeutic vaccination in the mouse oral cancer (MOC) 22 model. Two distinct MOC22 derived SLPs were tested - a TSA-oriented mutant intercellular adhesion molecule 1 (mICAM1) and p15E, an ERV encoded antigen. In silico prediction revealed mICAM1 SLP bore strong MHC-I and MHC-II epitopes sharing a mutant residue with vaccination significantly increasing both antigen-specific IFN-γ producing CD4 + and CD8 + T cells. By contrast, p15E SLP had a predicted high-affinity MHC-I epitope but lacked an MHC-II epitope and vaccination induced antigen-specific CD8 + but not CD4 + T cell responses. Therapeutic mICAM1 vaccination attenuated tumor growth effectively with mICAM1-specific T cells displaying durable IFN-γ production compared with p15E SLP. Furthermore, mICAM1 SLPs carrying weakened MHC-II binding epitopes were unable to control tumor growth. These data underscore the potential value of therapeutic targeting of HNSCC epitopes and highlight the importance of studying distinct antigen classes in this setting. Moreover, they raise the possibility that, at least in part, CD4 + T cell help is critical for cancer vaccination in this preclinical HNSCC model and suggest in silico prediction approaches prioritize overlapping MHC-I and MHC-II epitopes to generate potent cancer vaccines., Competing Interests: RU serves on a Merck scientific advisory board. The MOC models developed by RU have been filed with the Washington University Office of Technology Management and are currently licensed for distribution by Kerafast., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Purpose: In a head and neck squamous cell carcinoma (HNSCC) "window of opportunity" clinical trial, we reported that trametinib reduced MEK-Erk1/2 activation and resulted in tumor responses in a subset of patients. Here, we investigated resistance to trametinib and molecular correlates in HNSCC cell lines and patient samples., Experimental Design: HNSCC cell lines were treated with trametinib to generate resistant lines. Candidate bypass pathways were assessed using immunoblotting, CRISPR knockout, and survival assays. Effectiveness of combined trametinib and verteporfin targeting was evaluated. Patient-derived xenografts (PDXs) from responder patients were treated with trametinib and resistant tumors were analyzed. Window trial clinical samples were subjected to whole-exome and RNA sequencing., Results: HNSCC cell lines developed resistance (CAL27-TR and HSC3-TR) after prolonged trametinib exposure. Downstream effectors of the Hippo pathway were activated in CAL27-TR and HSC3-TR, and combined trametinib and verteporfin treatment resulted in synergistic treatment response. We defined the Hippo pathway effector Yap1 as an induced survival pathway promoting resistance to trametinib in HSC3-TR. Yap1 was necessary for HSC3-TR trametinib resistance, and constitutively active Yap1 was sufficient to confer resistance in parental HSC3. Analysis of trametinib neoadjuvant trial patient tumors indicated canonical MEK-Erk1/2 pathway activating mutations were infrequent, and Yap1 activity increased following trametinib treatment. Trametinib treatment of a PDX from a responder patient resulted in evolution of resistance with increased Yap1 expression and activity., Conclusions: These studies identify a Yap1-dependent resistance to trametinib therapy in HNSCCs. Combined Yap1 and MEK targeting may represent a strategy to enhance HNSCC response., (©2021 American Association for Cancer Research.)