Digital Commons Network^™

Folliculin Depletion Results In Liver Cell Damage And Cholangiocarcinoma Through Mit/Tfe Activation, Bruno Maria Custode, Francesco Annunziata, Felipe Dos Santos Matos, Valentina Schiano, Veronica Maffia, Milena Lillo, Rita Colonna, Rossella De Cegli, Andrea Ballabio, Nunzia Pastore

Duncan NRI Faculty and Staff Publications

Mutations in the tumor suppressor gene Folliculin (FLCN) are responsible for Birt-Hogg-Dube’ (BHD) syndrome, a rare inherited condition that predisposes affected individuals to skin tumors, pulmonary cysts, and kidney tumors. FLCN regulates key cellular pathways, including TFEB, TFE3, and mTORC1, which are critical for maintaining cell homeostasis. Loss of FLCN leads to both hyperactivation of mTORC1 and constitutive activation of TFEB and TFE3, contributing to tumorigenesis. While previous studies showed that Flcn liver-specific conditional knockout (FlcnLiKO) mice are protected from developing liver fibrosis and damage upon high-fat diet exposure, the potential role of FLCN loss in liver carcinogenesis …

Molecular Maestro In The Lung: The Sphingolipid Rheostat, Joselyn Rojas-Quintero, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Sugar Functionalized Collagen Material For Local Modulation Of Innate Immunity, Francesca Taraballi, Claudia Corbo, Julia Enterria-Rosales, John Otto Martinez, Silvia Minardi, Laura Pandolfi, Xing Wang, Ennio Tasciotti, Kavindra V Singh, Cesar A Arias, Bruna Corradetti

Faculty, Staff and Students Publications

Small alterations during the early stages of the innate immune response to an implant can drive large changes in adaptive immunity. Biomaterials for regenerative purposes can be engineered to modulate this immune response in beneficial ways. This study presents an innovative patch designed and functionalized to target the innate immunity at the implant site. Mannose moieties are incorporated into collagen patches, resulting in a technology called Local Immunotuning Patch (LIP), designed to directly interact with antigen presenting cells through their mannose receptor. In vitro, LIP shows anti-inflammatory effects on bone marrow-derived macrophages and inhibitory properties even on methicillin-resistant bacterial strains. …

Assessing And Developing Higher Education Faculty Digital Competency For Workplace Preparation In A Digital Society, Yolanda T. Martinez

Electronic Theses and Dissertations

A shared global theme across higher education institutions is the need for training and development regarding digital competencies for higher education, yet there are little to no digital competency frameworks for faculty at higher educational institutions, like there are for K12. What can leaders in higher educational institutions do to prepare adult learners for a digital society and workplace that continues to expand globally in every field? Should every school adopt XYZ College’s approach, where leadership collaborated and developed an emerging technologies academy (ETA) to provide support and training on emerging technologies provided and supported by the college to self-enrolled …

Electronic Health Record Downtime, Grace R. Baldauf

Electronic Theses and Dissertations

Electronic health record (EHR) downtime presents significant challenges to patient safety and care quality in acute care settings, particularly regarding timely medication administration. This project addressed the problem of late or absent medication doses during planned or unplanned EHR downtime. The investigator aimed to evaluate the effectiveness of a structured downtime plan in improving nurses’ ability to administer medications on time during periods of EHR unavailability. The investigator used a quantitative design to implement a downtime plan evaluation paradigm. Data were collected using retrospective chart reviews of medication administration records pre-implementation and postimplementation of the downtime plan. The sample included …

Institutional Betrayal And Military Vaccine Mandates: An Inquiry Into Loss Of Health Autonomy Concerning Unlimited Liability Contractual Employment In The Covid-19 Era, Aaron G. Dehaven

Electronic Theses and Dissertations

The balance between government control and personal liberty is a growing concern in the modern world. Nowhere is this more evident than in discussions surrounding government policy in public health and individual health autonomy. The Covid-19 pandemic forced many institutions to change their standard operating procedures by adapting to rapidly changing health guidance instituted to protect public health. These changes highlighted the role of health autonomy and individuals’ rights to refuse medical treatments. The Department of Defense changed many aspects of how it operated during the pandemic, including the mandate of the Covid-19 vaccine for all service members. For various …

Perceived Leadership Behaviors And Workplace Motivation: The Predictive Role Of Generational Cohorts In The U.S. Construction Industry, Leslie D. Klinegardner

Electronic Theses and Dissertations

The purpose of this study was to examine the extent to which perceived leadership behaviors predicted workplace motivation among construction workers across generational cohorts in the Greater Houston, Texas area. Grounded in self-determination theory, the research explored how transformational, transactional, and passive-avoidant leadership behaviors predicted the satisfaction and frustration of psychological needs for autonomy, competence, and relatedness. The analysis also considered whether leadership behaviors and generational cohort served as significant predictors of workplace motivation outcomes. The study followed a quantitative, predictive, cross-sectional design using survey methodology. Data were collected using the Multifactor Leadership Questionnaire (MLQ) and the Basic Psychological Need …

Mechanisms Underlying Atrial Fibrillation In Chronic Kidney Disease, Jose Alberto Navarro-Garcia, Joshua A Keefe, Jia Song, Na Li, Xander H T Wehrens

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) is a serious and progressive worldwide health problem affecting 15 % of the global population. CKD is associated with higher mortality rates due to secondary complications such as cardiovascular disease. Common cardiovascular complications found in CKD patients include left ventricular hypertrophy, heart failure, and cardiac arrhythmias. The most common type of cardiac arrhythmia in CKD patients is atrial fibrillation (AF). Proper management of AF is important due to its high risk of cardiovascular complications and stroke. The incidence of AF remains higher in CKD patients than in the healthy population, highlighting the need to improve our …

Anaphylaxis Definition, Overview, And Clinical Support Tool: 2024 Consensus Report-A Ga2len Project, Timothy E Dribin, Antonella Muraro, Carlos A Camargo, Paul J Turner, Julie Wang, Graham Roberts, Aikaterini Anagnostou, Susanne Halken, Jay Liebermann, Margitta Worm, Torsten Zuberbier, Hugh A Sampson, Ga(2)Len Anaphylaxis Study Team

Faculty, Staff and Students Publications

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes.

Objective: We sought to develop a consensus anaphylaxis definition, overview, and clinical support tool.

Methods: A 12-member writing group developed draft outputs modified with input from a 46-member international expert panel, 31 medical stakeholder organizations, and 15 patient advocacy organizations. The expert panel participated in a modified Delphi process to seek consensus …

An Electronic Trigger To Detect Telemedicine-Related Diagnostic Errors, Daniel R Murphy, Himabindu Kadiyala, Li Wei, Hardeep Singh

Faculty, Staff and Students Publications

Introduction

Methods

Low-Dose Metformin Requires Brain Rap1 For Its Antidiabetic Action, Hsiao-Yun Lin, Weisheng Lu, Yanlin He, Yukiko Fu, Kentaro Kaneko, Peimeng Huang, Ana B De La Puente-Gomez, Chunmei Wang, Yongjie Yang, Feng Li, Yong Xu, Makoto Fukuda

Faculty, Staff and Students Publications

Metformin is the most commonly prescribed antidiabetes drug, yet its precise mechanism of action remains controversial. Previous studies have suggested that metformin acts peripherally by reducing hepatic glucose output and altering gut functions. Here, we report a neural mechanism via the small guanosine triphosphatase Ras-related protein 1 (Rap1). Mice with forebrain-specific Rap1 knockout exhibited resistance to the antidiabetic effects of low-dose metformin while remaining sensitive to other antidiabetic agents. Centrally administered metformin inhibited brain Rap1 and reduced hyperglycemia. Conversely, forced activation of brain Rap1 increased glycemia and abolished the glycemic effect of metformin. Metformin activated a specific subset of neurons …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder: An Enigma-Pgc Ptsd Study, Carissa W Tomas, Jacklynn M Fitzgerald, C Lexi Baird, Courtney C Haswell, Chadi G Abdallah, Michael Angstadt, Justin T Baker, Hannah Berg, Jennifer U Blackford, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Terri A Deroon-Cassini, Seth G Disner, Wissam El Hage, Negar Fani, Jessie L Frijling, Evan M Gordon, Daniel W Grupe, Xiaofu He, Ryan Herringa, David Hofmann, Ashley A Huggins, Ahmed Hussain, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa L Kaufman, Yoojean Kim, Anthony King, Saskia B J Koch, Sheri Koopowitz, Amit Lazarov, Lauren A M Lebois, Isreal Liberzon, Shmuel Lissek, Antje Manthey, Geoffrey May, Katie A Mclaughlin, Laura Nawijn, Steven M Nelson, Yuval Neria, Jack B Nitschke, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, Yann Quidé, Orren Ravid, Kerry Ressler, Marisa Ross, Lauren E Salminen, Kelly Sambrook, Chiahao Shih, Anika Sierk, Scott R Sponheim, Dan J Stein, Jennifer Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Paul M Thompson, Nic J A Van Der Wee, Steven J A Van Der Werff, Sanne J H Van Rooij, Mirjam Van Zuiden, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Xin Wang, Hong Xie, Xi Zhu, Sigal Zilcha-Mano, Christine L Larson, Rajendra Morey

Faculty, Staff and Students Publications

Using functional magnetic resonance imaging (fMRI), symptoms of posttraumatic stress disorder (PTSD) have been associated with aberrations in brain networks in the absence of a given cognitive demand or task, called resting-state networks. Prior work has focused on disruption in the static functional connectivity (FC) among specific regions constrained by a priori hypotheses. However, dynamic FC, an approach that examines brain network characteristics over time, may provide a more sensitive measure to understand the network properties underlying dysfunction in PTSD. Further, using a data-driven analytic approach may reveal the contribution of other larger network disturbances beyond those revealed by hypothesis-driven …

Exploring Behavioural Motivations Of Treatment Refusal In Cancer: A Q-Methodological Approach, Ruby Koyllor A. Gleeson, Nicolas H. Hart, Darren Haywood, Frank D. Baughman

Research outputs 2022 to 2026

Background: Cancer treatment refusal is known to lower survival rates and increase cancer symptoms in individuals with cancer. Behavioural motivations of treatment refusal need to be elucidated for better cancer care. Using Q-methodology, a mixed methods research approach, we explored behavioural motivations of treatment refusal in individuals diagnosed with cancer. Method: Thirty-nine individuals (n = 39; age = 49.2 ± 12.2 years) were recruited from Australia, the UK, and the USA, who had refused cancer treatment within the past decade. Participants completed an online demographic questionnaire and a Q-sort activity which required the organisation and ranking of 44 statements on …

The Moderating Effect Of Dietary Patterns On The Association Of Depression And Anxiety With Cognitive Function, Hilal Salim Said Al Shamsi, Samantha L. Gardener, Hamid R. Sohrabi, Kevin Taddei, Colin L. Masters, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.B. Fernando

Research outputs 2022 to 2026

Background and aims: Investigating modifiable risk factors, such as diet, is crucial in understanding their effects on the relationship between Alzheimer's disease (AD)-related cognitive decline and related conditions. This study assesses whether dietary patterns moderate the relationship between symptoms of depression, anxiety, and cognitive function in older adults. Given that biological and psychosocial differences between sexes may influence dietary behaviours, mental health symptoms, and cognitive outcomes, conducting sex-stratified analyses will allow for identification of differential associations. Method: Cross-sectional data from cognitively unimpaired older adults (n = 1174, age ≥60 years) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were …

Mining Waste In Asphalt Pavements: A Critical Review Of Waste Rock And Tailings Applications, Adeel Iqbal, Nuha S. Mashaan, Themelina Paraskeva

Research outputs 2022 to 2026

This paper presents a critical and comprehensive review of the application of mining waste, specifically waste rock and tailings, in asphalt pavements, with the aim of synthesizing performance outcomes and identifying key research gaps. A systematic literature search yielded a final dataset of 41 peer-reviewed articles for detailed analysis. Bibliometric analysis indicates a notable upward trend in annual publications, reflecting growing academic and practical interest in this field. Performance-based evaluations demonstrate that mining wastes, particularly iron and copper tailings, have the potential to enhance the high-temperature performance (i.e., rutting resistance) of asphalt binders and mixtures when utilized as fillers or …

Behaviour Change Design For Reducing Plastic Usage By Perceived Similarity Nudge, Quentin Ehkirch, Ferdi Raharja, Udari Samaranayake, Ken Ichi Sawai, Akane Matsumae

Research outputs 2022 to 2026

This study explores the influence of perceived similarity on pro-environmental behavior, focusing on plastic reduction. Participants' daily plastic use and reduction were tracked over 30 days via online chat software, with controlled nudges from an agent. Each group included two examinees and one agent. Behavioral data were analyzed to evaluate predictability from various perspectives and its relationship with behavioral change. Results showed significant differences in predictability based on perceived similarity, particularly during the first 10 days. Furthermore, nudges, consumption levels, and behavioral changes significantly affected predictability within the first 20 days. These findings contribute to understanding how perceived similarity can …

A Superhypersoft Set-Based Analysis Framework For Innovation And Entrepreneurship Development In Higher Vocational Colleges: An Industry-Sector Integration Perspective, Bingmeng Mao

Neutrosophic Sets and Systems

No abstract provided.

A Hybrid Neutrosophic Statistical–Game Theoretic Framework For Modeling Green Policy Dynamics Of Coal Mining Enterprises Under Indeterminacy In Resource-Based Regions, Ruifen Zhao

Neutrosophic Sets and Systems

No abstract provided.

Systems Statistical Engineering – Hierarchical Fuzzy Constraint Propagation, Hengameh Fakhravar

Engineering Management & Systems Engineering Theses & Dissertations

Driven by the growing need in the 21st century for integrating rigorous statistical analysis into engineering research, there is a movement to develop an integrated statistical engineering science within statistics and quality communities (Hoerl & Snee, 2010; Anderson-Cook et al., 2012). Systems Statistical Engineering research seeks to integrate the Causal Bayesian hierarchical modeling (Pearl, 2009) and cybernetic control theory within Beer’s Viable System Model (1972, 1979, 1985) and the Complex Systems Governance framework (Keating, 2014; Keating & Katina, 2015, 2016) to produce multivariate systemic models for robust dynamic systems mission performance. Cotter & Quigley (2018) set forth the Bayesian systemic …

Using Equivalence-Based Instruction And Behavioral Skills Training To Teach Social Skills, Alexander Orzeck

Theses

Social skills are an integral part of human life, so it stands to reason that teaching methodologies should be developed to instruct people in this complex topic. One method to teach social skills has been behavioral skills training, in which the four-step sequence of vocal and written instruction, modeling, roleplay, and feedback exposes learners to the social concepts until a mastery criterion is reached. Skills relevant to socialization have also been taught with equivalence-based instruction, in which the concept of stimulus equivalence is employed to generate novel relations between stimuli for the purpose of teaching some skill. No instance was …

College Leaders’ Perspectives Of Diversity At A Community College System In Texas: A Phenomenological Study Of Validation, Xandelyn Wright Washington

All Dissertations

The United States has undergone dramatic changes in student demographics over the last 40 years. Nowhere is this reflected more than in the field of education (Center for Public Education, 2012; Fabina et al., 2023). Disaggregation of student demographics is a useful and common method for measuring student outcomes, and in the United States, non-majority students consistently have lower student outcomes (Gay, 2013; Howard, 2010; Ocay et al., 2023).

Ma and Baum (2016) and McNair et al. (2015) stated that the role of community colleges is pivotal in postsecondary education. As such, college leaders and administrators have focused attention on …

Stress-Survival Pathway Genes In Colorectal Cancer: Crc Progression And Hispanic Disparities, Highlighting Mcm10 As A Potential Player, Urbashi Basnet

Open Access Theses & Dissertations

Despite advances in screening and treatment, colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the U.S., with notable disparities across racial and ethnic groups. Hispanic populations face a disproportionate burden, underscoring significant differences in incidence and outcomes. This study examines the role of the Stress-Survival Pathway (SSP) in colorectal cancer (CRC), with a focus on addressing health disparities among Hispanic populations. Twenty-eight differentially expressed SSP genes identified from bioinformatic analysis were validated in CRC cell lines and cDNA arrays using qRT-PCR and tissue microarrays by immunohistochemistry. SSP genes were further analyzed in CRC tissues from Hispanic and …

The Relationship Between Inclusive Classroom Practices, Stem Identity And Stem Interest In Latinx Secondary Students, Laura Corral Carrillo

Open Access Theses & Dissertations

Latinx students remain underrepresented in science, technology, engineering, and mathematics (STEM) fields despite representing a growing portion of the U.S. school population. Research suggests that inclusive classroom practices (ICPs) that affirm students' cultural and linguistic identities can play a critical role in shaping STEM identity and fostering interest in STEM pathways. This mixed-methods study investigated the relationship between ICPs, Latinx high school students' STEM identity development, and their interest in pursuing STEM careers in the Texas borderlands. The study employed a convergent design, integrating quantitative survey data from 52 students and qualitative interview data from four secondary science teachers. Quantitative …

The Origin And Geologic History Of Dolostones Associated With The Moab Valley Salt Wall, Paradox Basin, Utah, Charles Ojodale Igomu, Charles Ojodale Igomu

Open Access Theses & Dissertations

This thesis investigates the origin and geologic context of dolostones associated with the Moab Valley salt wall in southeastern Utah, a feature within the broader Paradox Basin that offers an exceptional opportunity to study the interplay between carbonate sedimentation, diagenesis, and salt diapirism. The fundamental research question focuses on evaluating whether dolostones observed in the Moab Valley are all depositional, diagenetic or structurally reworked components of deeper stratigraphy, and how their presence and geometry relate to the halokinetic processes that shaped sedimentation across the Moab Valley. This study tested the hypothesis that dolostones within Moab Valley represent a mixed assemblage …

Judicial And Techno-Securitization Of Immigration: Narratives De Filosofia De Inmigracion Y Justicia, Mohammad Rubaiyat Rahman

Open Access Theses & Dissertations

In the thesis, I develop a philosophical account which is centered on immigration enforcement discrimination, surveillance and procedural justice. The thesis propounds two arguments. The first argument contends that the immigration enforcement of the United States (U.S.), including the use of surveillance technology, contributes to the structural injustice. The second argument is that the U.S. immigration surveillance and immigration enforcement should be qualified by procedural justice and constitutional democracy.

The thesis prioritizes the practice of the U.S. immigration policy, enforcement and how these promote structural injustice against non-citizens and citizens, specifically those who are Latinos living in the U.S.-Mexico borderlands. …

Model-Based Systems Engineering For Aerospace Applications: Strategic Requirements Prioritization In Complex Adaptive Systems And Digital Integration, Iqtiar Md Siddique

Open Access Theses & Dissertations

Ineffective systems engineering practices continue to jeopardize aerospace missions, resulting in multi-billion-dollar losses, delays, and fragmented development outcomes. As complexity intensifies and timelines shrink, conventional document-based methods increasingly fail to support early validation, cross-domain traceability, and synchronized tool usage. This research presents an integrated approach that addresses three critical gaps: synchronizing executable and traceable MBSE models across structural, behavioral, and requirements domains; applying scalable requirements prioritization techniques tailored for Complex Adaptive Systems; and establishing automated simulation feedback loops through digital toolchain integration. Central to this strategy is the Digital Trinity, which connects system models, simulations, and lifecycle data through a …

Addressing Challenges In Developing Treatments For Inherited Retinal Diseases: Recommendations From The Third Monaciano Symposium, Debra A Thompson, K Thiran Jayasundera, Oleg Alekseev, Robin R Ali, Alessia Amato, Vadim Y Arshavsky, Isabelle S Audo, Alberto Auricchio, James W B Bainbridge, Eyal Banin, Cagri G Besirli, David G Birch, Kari E Branham, Artur V Cideciyan, Stephen P Daiger, Jacque L Duncan, Abigail T Fahim, John G Flannery, Roberto Gattegna, John R Heckenlively, Elise Héon, Alessandro Iannaccone, Naheed W Khan, Samer Khateb, Henry J Klassen, Bart P Leroy, Dario Marangoni, Michel Michaelides, David C Musch, Mark E Pennesi, Simon M Petersen-Jones, Eric A Pierce, Rajesh C Rao, José-Alain Sahel, Paul A Sieving, Enrica Strettoi, Cameron R Strong, Thomas J Wubben, Paul Yang, David N Zacks

Faculty, Staff and Student Publications

Over the past decade, efforts focused on developing genetic therapies for inherited retinal diseases have advanced steadily to clinical trials and the development of a treatment, fueling optimism for the potential of precision medicines to provide safe and effective therapies for these rare conditions. Although several ongoing programs remain poised for success, numerous challenges have negatively impacted the ability to obtain regulatory approvals. The present position paper briefly summarizes recent advances and challenges in developing therapeutics for inherited retinal diseases, and presents a set of recommendations for moving the field forward. The priorities identified are discussed in terms of progress …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …

Acquired Resistance In Cancer: Towards Targeted Therapeutic Strategies, Alice Soragni, Erik S Knudsen, Thomas N O'Connor, Cristina E Tognon, Jeffrey W Tyner, Beatrice Gini, Donghwa Kim, Trever G Bivona, Xingxing Zang, Agnieszka K Witkiewicz, David W Goodrich, Dadi Jiang, Seth T Gammon, Christopher D Willey, Paul C Boutros, Vlad C Sandulache, Abdullah A Osman, Jeffrey N Myers, Kamiya Mehla, Pankaj K Singh, Keith S Chan, Hongbo Gao, Himangi Marathe

Faculty, Staff and Student Publications

Development of acquired therapeutic resistance limits the efficacy of cancer treatments and accounts for therapeutic failure in most patients. How resistance arises, varies across cancer types and differs depending on therapeutic modalities is incompletely understood. Novel strategies that address and overcome the various and complex resistance mechanisms necessitate a deep understanding of the underlying dynamics. We are at a crucial time when innovative technologies applied to patient-relevant tumour models have the potential to bridge the gap between fundamental research into mechanisms and timing of acquired resistance and clinical applications that translate these findings into actionable strategies to extend therapy efficacy. …

Molecular Determinants Of Sotorasib Clinical Efficacy In Krasg12c-Mutated Non-Small-Cell Lung Cancer, Ferdinandos Skoulidis, Bob T Li, Adrianus Johannes De Langen, David S Hong, Herve Lena, Juergen Wolf, Grace K Dy, Alessandra Curioni Fontecedro, Pascale Tomasini, Vamsidhar Velcheti, Anthonie J Van Der Wekken, Christophe Dooms, Luis Paz-Ares Rodriguez, Giannis Mountzios, Adrian Sacher, Ernest Nadal, Sebastien Couraud, Sang-We Kim, Kenneth O'Byrne, Danilo Rocco, Ryo Toyozawa, Izabela Chmielewska, Colin R Lindsay, Antreas Hindoyan, Lata Mukundan, Tomasz Wilmanski, Abraham Anderson, Christine Ardito-Abraham, Amrita Pati, Anita Reddy, Bhakti Mehta, Martin Schuler

Faculty, Staff and Student Publications

Molecular determinants of KRAS(G12C)inhibitor efficacy in KRASG12C-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRASG12C-mutated NSCLC co-mutational subsets and transcriptional subtypes. We also identify low expression of TTF1 and KEAP1 co-mutations/NRF2 activation as major determinants of sotorasib anti-tumor efficacy and adverse prognostic features. Exploratory analyses highlight potential tumor cell-extrinsic contributors to sotorasib anti-tumor activity and suggest …