Dissecting the oncogenic properties of essential RNA-modifying enzymes: a focus on NAT10.

Chemical modifications of ribonucleotides significantly alter the physicochemical properties and functions of RNA. Initially perceived as static and essential marks in ribosomal RNA (rRNA) and transfer RNA (tRNA), recent discoveries unveiled a dynamic landscape of RNA modifications in messenger RNA (mRNA) and other regulatory RNAs. These findings spurred extensive efforts to map the distribution and function of RNA modifications, aiming to elucidate their distribution and functional significance in normal cellular homeostasis and pathological states. Significant dysregulation of RNA modifications is extensively documented in cancers, accentuating the potential of RNA-modifying enzymes as therapeutic targets. However, the essential role of several RNA-modifying enzymes in normal physiological functions raises concerns about potential side effects. A notable example is N-acetyltransferase 10 (NAT10), which is responsible for acetylating cytidines in RNA. While emerging evidence positions NAT10 as an oncogenic factor and a potential target in various cancer types, its essential role in normal cellular processes complicates the development of targeted therapies. This review aims to comprehensively analyze the essential and oncogenic properties of NAT10. We discuss its crucial role in normal cell biology and aging alongside its contribution to cancer development and progression. We advocate for agnostic approaches to disentangling the intertwined essential and oncogenic functions of RNA-modifying enzymes. Such approaches are crucial for understanding the full spectrum of RNA-modifying enzymes and imperative for designing effective and safe therapeutic strategies.

Variation in external beam treatment plan quality: An inter-institutional study of planners and planning systems.

PURPOSE: This study quantifies variation in radiation treatment plan quality for plans generated by a population of treatment planners given very specific plan objectives. METHODS AND MATERIALS: A "Plan Quality Metric" (PQM) with 14 submetrics, each with a unique value function, was defined for a prostate treatment plan, serving as specific goals of a hypothetical "virtual physician." The exact PQM logic was distributed to a population of treatment planners (to remove ambiguity of plan goals or plan assessment methodology) as was a predefined computed tomographic image set and anatomic structure set (to remove anatomy delineation as a variable). Treatment planners used their clinical treatment planning system (TPS) to generate their best plan based on the specified goals and submitted their results for analysis. RESULTS: One hundred forty datasets were received and 125 plans accepted and analyzed. There was wide variability in treatment plan quality (defined as the ability of the planners and plans to meet the specified goals) quantified by the PQM. Despite the variability, the resulting PQM distributions showed no statistically significant difference between TPS employed, modality (intensity modulated radiation therapy versus arc), or education and certification status of the planner. The PQM results showed negligible correlation to number of beam angles, total monitor units, years of experience of the planner, or planner confidence. CONCLUSIONS: The ability of the treatment planners to meet the specified plan objectives (as quantified by the PQM) exhibited no statistical dependence on technologic parameters (TPS, modality, plan complexity), nor was the plan quality statistically different based on planner demographics (years of experience, confidence, certification, and education). Therefore, the wide variation in plan quality could be attributed to a general "planner skill" category that would lend itself to processes of continual improvement where best practices could be derived and disseminated to improve the mean quality and minimize the variation in any population of treatment planners.