Genetic Phenomena Commons^™

Editorial: Advances And Methods In Mesenchymal Stem Cells, Pamela L Wenzel

Faculty, Staff and Student Publications

No abstract provided.

An Image-Driven Micromechanical Approach To Characterize Multiscale Remodeling In Infarcted Myocardium, Emilio A Mendiola, Sunder Neelakantan, Qian Xiang, Shuda Xia, Jianyi Zhang, Vahid Serpooshan, Peter Vanderslice, Reza Avazmohammadi

Faculty, Staff and Student Publications

Myocardial infarction (MI) is accompanied by the formation of a fibrotic scar in the left ventricle (LV) and initiates significant alterations in the architecture and constituents of the LV free wall (LVFW). Previous studies have shown that LV adaptation is highly individual, indicating that the identification of remodeling mechanisms post-MI demands a fully subject-specific approach that can integrate a host of structural alterations at the fiber-level to changes in bulk biomechanical adaptation at the tissue-level. We present an image-driven micromechanical approach to characterize remodeling, assimilating new biaxial mechanical data, histological studies, and digital image correlation data within an in-silico framework …

Perceptions Of The Addictiveness Of Low-Nicotine Cigarettes Versus Typical Cigarettes And Exposure To Tobacco Industry-Sponsored Corrective Campaign, Onyema Greg Chido-Amajuoyi, Dale S Mantey, Efehi Igbinomwanhia, Onyinye Omega-Njemnobi, Henry Onyeaka, Robert K Yu, Israel Agaku, Sanjay Shete

Faculty, Staff and Student Publications

Background: In 2017, the U.S. Food and Drug Administration (FDA) announced a regulatory plan to reduce the nicotine content of cigarettes. This study examines the association of exposure to industry-sponsored corrective statements on perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes within the general US population.

Methods: The study comprised 4975 US adult respondents of the 2019 Health Information National Trends Survey (HINTS 5, Cycle 3). Multinomial logistic regression models were used to examine associations between exposure to tobacco industry corrective messages and perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes.

Results: In the …

Explainable Suicide Phenotyping From Initial Psychiatric Evaluation Notes Using Reasoning Large Language Models, Zehan Li, Wanjing Wang, Lokesh Shahani, Rodrigo M Vieira, Salih Selek, Jair Soares, Hongfang Liu, Ming Huang

Faculty, Staff and Student Publications

Clinical phenotyping is the process of extracting patient's observable symptoms and traits to better understand their disease condition. Suicide phenotyping focuses more on behavioral and cognitive characteristics, such as suicide ideation, attempt, and self-injury, to identify suicide risks and improve interventions. In this study, we leveraged the latest reasoning models, namely 4o, o1, and o3-mini, to perform note-level multi-label classification and reasoning generation tasks using previously annotated psychiatric evaluation notes from a safety-net psychiatric inpatient hospital in Harris County, Texas. Compared with the previously finetuned GPT-3.5 model, the out-of-box reasoning models prompted with in-context learning achieved comparable and better performance, …

Monet: A Database For Prediction Of Neoantigens Derived From Microsatellite Loci, Nan Deng, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

BACKGROUND: Microsatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET).

METHOD: MONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using …

Are Published Cancer Care Trial Protocols With Traditional Chinese Medicine Interventions Concordant With Spirit-Tcm Extension 2018? A Scoping Review On Published Trial Protocols Between 2019 And 2022, Hezheng Lai, Peiying Yang, Xin Shelley Wang, David Lim, Anderson Lam, Yucong Shi, Yishi Huang, Xiaoshu Zhu

Faculty, Staff and Student Publications

BACKGROUND: The SPIRIT-TCM Extension 2018 was created to guide the design and reporting of Traditional Chinese Medicine (TCM) clinical trial protocols. This study aims to investigate the extent of concordance with this guideline in the relevant field of cancer care research.

METHODS: A scoping review of TCM cancer trial protocols published in English and Chinese since January 2019 was conducted. Five major academic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, and China National Knowledge Infrastructure) were searched. Concordance with the SPIRIT-TCM Extension 2018 was assessed by descriptive analysis.

RESULTS: Fifty-three TCM cancer care trial protocols were identified, comprising 23 acupuncture, 26 Chinese …

Postmortem-Derived Ipsc Models In Substance Use Disorders Research, Emily Frances Mendez, Consuelo Walss-Bass

Faculty, Staff and Student Publications

No abstract provided.

Correction To: Egfr Tyrosine Kinase Inhibitors For The Treatment Of Metastatic Non‑Small Cell Lung Cancer Harboring Uncommon Egfr Mutations: A Podcast, Xiuning Le, Eric Nadler, Daniel B Costa, John Victor Heymach

Faculty, Staff and Student Publications

No abstract provided.

Her4 And Egfr Activate Cell Signaling In Nrg1 Fusion-Driven Cancers: Implications For Her2-Her3-Specific Versus Pan-Her Targeting Strategies, Hibiki Udagawa, Monique B Nilsson, Jacqulyne P Robichaux, Junqin He, Alissa Poteete, Hong Jiang, Simon Heeke, Yasir Y Elamin, Yuji Shibata, Shingo Matsumoto, Kiyotaka Yoh, Shogo Okazaki, Takashi Masuko, Igor Odintsov, Romel Somwar, Marc Ladanyi, Koichi Goto, John V Heymach

Faculty, Staff and Student Publications

Introduction: NRG1 gene fusions are clinically actionable alterations identified in NSCLC and other tumors. Previous studies have reported that NRG1 fusions signal through HER2 and HER3 but, thus far, strategies targeting HER3 specifically or HER2-HER3 signaling have exhibited modest activity in patients with NSCLC bearing NRG1 fusions. Although NRG1 fusion proteins can bind HER4 in addition to HER3, the contribution of HER4 and other HER family members in NRG1 fusion-positive cancers is not fully understood.

Methods: We investigated the role of HER4 and EGFR-HER3 signaling in NRG1 fusion-positive cancers using Ba/F3 models engineered to express various HER family members in …

Establishment Of A Brain Tumor Consortium Of Africa: Advancing Collaborative Research And Advocacy For Brain Tumors In Africa, Lateef A Odukoya, Kwadwo Darko, Francis Zerd, Nathalie C Ghomsi, Gloria Kabare, David O Kamson, Jeanette E Eckel-Passow, Robert B Jenkins, Gaspar J Kitange, Andrea O Akinjo, Kabir B Badmos, Olufemi Bankole, Olufemi E Idowu, Claire Karekezi, Elias Edrick, Chukwuyem Ekhator, Victoria M Katasi, Desmond A Brown, Jason Huse, Henry Llewellyn, Margreth Magambo, Michael Magoha, Umaru Barrie, Advera Ngaiza, Arsene D Nyalundja, Minda Okemwa, Lawrence Osei-Tutu, Bernard Petershie, W Elorm Yevudza, Charles C Anunobi, Liadi Tiamiyu, Gbetoho Fortuné Gankpe, Kashaigili Heronima, Dominique Higgins, Kristin Schroeder, Teddy Totimeh, James Balogun, Beverly Cheserem, Arnold B Etame, Ekokobe Fonkem

Faculty, Staff and Student Publications

Background: Brain tumors represent a significant global health challenge, with rising incidence and mortality impacting individuals worldwide and contributing to cancer-related morbidity and mortality. In Africa, this burden is exacerbated by limited access to advanced diagnostics, treatment options, and multidisciplinary care, compounded by the absence of standardized cancer registration and tumor biobanking. The introduction of molecular diagnostics, as outlined in the 2021 World Health Organization central nervous system (CNS) tumor classification, adds complexity to brain tumor management, particularly in regions with scarce resources.

Methods: To address these issues, the Brain Tumor Consortium for Africa (BTCA) was established in 2023, bringing …

Circulating Cancer-Associated Macrophage-Like Cells And Macrophage-Related Cytokines In Obese Patients With Advanced Breast Cancer Who Undergo Neoadjuvant Chemotherapy, Toshiaki Iwase, Aaroh Parikh, Dong Wenli, Yu Shen, Daniel L Adams, Cha-Mei Tang, Evan N Cohen, James M Reuben, Tushaar Vishal Shrimanker, Sudpreeda Chainitikun, Kumiko Kida, Akshara Singareeka Raghavendra, Maryanne E Sapon, Onur Sahin, Anjali James, Nithya Sridhar, Ann H Klopp, Debasish Tripathy, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Cancer-associated macrophage-like cells (CAMLs) are rare, gigantic, and atypical circulating cells found exclusively in the peripheral blood of patients with solid cancers. Obesity-induced hypoxia attracts macrophages to the tumor microenvironment, where they contribute to establishing chronic inflammation, leading to cancer progression. We hypothesized that obese patients with advanced breast cancer may have CAML profiles different from those of nonobese patients, and these profiles may correlate with proinflammatory markers or other macrophage-related markers.

Methods: We prospectively collected 20 mL of peripheral blood from patients diagnosed with stage 2-4 breast cancer. We identified CAMLs using the CellSieve microfiltration system and in …

The Mir-17-92 Cluster In Cardiac Health And Disease, Yuhan Cao, Mingjie Zheng, Maham A Sewani, Jun Wang

Faculty, Staff and Student Publications

MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post-transcriptional regulation. The miR-17-92 cluster includes six individual members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1. The miR-17-92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR-17-92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR-17-92 …

Pathologic Processing Of Lung Cancer Resection Specimens After Neoadjuvant Therapy, Annikka Weissferdt, Cheuk H Leung, Heather Lin, Boris Sepesi, William N William, Stephen G Swisher, Tina Cascone, J Jack Lee, Abujiang Pataer

Faculty, Staff and Student Publications

Neoadjuvant treatment of non-small cell lung cancer challenges the traditional processing of pathology specimens. Induction therapy before resection allows evaluation of the efficacy of neoadjuvant agents at the time of surgery. Many clinical trials use pathologic tumor response, measured as major pathologic response (MPR, ≤10% residual viable tumor [RVT]) or complete pathologic response (CPR, 0% RVT) as a surrogate of clinical efficacy. Consequently, accurate pathologic evaluation of RVT is crucial. However, pathologic assessment has not been uniform, which is particularly true for sampling of the primary tumor, which instead of the traditional processing, requires different tissue submission because the focus …

Single-Molecule Fret Analyses Of Nmda Receptors, Ryan J Durham, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Single-molecule fluorescence resonance energy transfer (smFRET) enables the real-time observation of conformational changes in a single protein molecule of interest. These observations are achieved by attaching fluorophores to proteins of interest in a site-specific manner and investigating the FRET between the fluorophores. Here we describe the method wherein the FRET is studied by adhering the protein molecules to a slide using affinity-based interactions and measuring the fluorophores' fluorescence intensity from a single molecule over time. The resulting information can be used to derive distance values for a point-to-point measurement within a protein or to calculate kinetic transition rates between various …

Hormone Regulation Of Corticotropin-Releasing Factor Receptor 1 In The Female Mouse Brain, Rose M De Guzman, Jason S Jacobskind, Zachary J Rosinger, Krystyna A Rybka, Katherine E Parra, Aya L Caballero, Massoud S Sharif, Nicholas J Justice, Damian G Zuloaga

Faculty, Staff and Student Publications

Introduction: Corticotropin-releasing factor receptor 1 (CRFR1) is a key regulator of neuroendocrine and behavioral stress responses. Previous studies have demonstrated that CRFR1 in certain hypothalamic and preoptic brain areas is modified by chronic stress and during the postpartum period in female mice, although the potential hormonal contributors to these changes are unknown.

Methods: This study focused on determining the contributions of hormones associated with stress and the maternal period (glucocorticoids, prolactin, estradiol/progesterone) on CRFR1 levels using a CRFR1-GFP reporter mouse line and immunohistochemistry.

Results: Administration of dexamethasone, an agonist of the glucocorticoid receptor, elevated CRFR1 in the anteroventral periventricular nucleus …

Tissue Transglutaminase: A Multifunctional And Multisite Regulator In Health And Disease, Zhouzhou Yao, Yuhua Fan, Lizhen Lin, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulfide isomerase (PDI), a protein kinase, and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this …

Generation Of Non-Alloreactive Antiviral Central Memory Cd8 Human Veto T Cells For Cell Therapy, Esther Bachar-Lustig, Assaf Lask, Yaki Eidelstein, Noga Or-Geva, Rotem Gidron-Budovsky, Bar Nathansohn-Levy, Matthias Eyrich, Wei-Hsin Liu, Giang Dang, Karla Castro Miranda, Alejandro Ramirez, Indreshpal Kaur, Katayoun Rezvani, Elizabeth Shpall, Richard E Champlin, Arnon Nagler, Avichai Shimoni, Sivan Barnees-Kagan, Yair Reisner

Faculty, Staff and Student Publications

Previous studies in mice demonstrated that CD8 T cells exhibit marked veto activity enhancing engraftment in several models for T cell-depleted bone marrow (TDBM) allografting. To reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic CD8 veto T cells, these studies made use of naive CD8 T cells stimulated against third-party stimulators under cytokine deprivation and subsequent expansion in the presence of IL-15. More recently, it was shown that mouse CD8 veto T cells can be generated by stimulating CD8 memory T cells from ovalbumin immunized mice under cytokine deprivation, using ovalbumin as a third-party antigen. These cells also …

Differences In Connected Speech Outcomes Across Elicitation Methods, Tatiana T Schnur, Sharon Wang

Faculty, Staff and Student Publications

Background: Connected speech is often used to assess many aspects of an individual's language abilities after stroke. However, it is unknown the degree to which elicitation methods differ in generating structural and syntactic aspects of connected speech, two critical components of successful communication. Quantifying the degree to which elicitation methods differ in eliciting structurally, syntactically, and lexically complex connected speech at the earliest stage of stroke before reorganization and rehabilitation of function independent of clinical diagnosis of aphasia has not been examined to date. Addressing this gap has implications for early clinical intervention as well as empirical studies of connected …

Innovations In Molecular Biomarkers And Biomaterial-Based Immunotherapies For Head & Neck Cancer, Sarah Anne Wong, Victoria A Manon, Simon Young, Chi T Viet

Faculty, Staff and Student Publications

Purpose of review: Oral squamous cell carcinoma (OSCC) survival rates have remained stagnant due to a lack of targeted therapies and diagnostic tools. Patient risk is currently determined solely through clinicopathologic features, primarily tumor staging, which lacks the necessary precision to stratify patients by risk and accurately dictate adjuvant treatment. Similarly, conventional OSCC therapies have well-established toxicities and limited efficacy.

Recent findings: Recent studies show that patient risk can now be assessed using non-invasive techniques, at earlier time points, and with greater accuracy using molecular biomarker panels. Additionally, novel immunotherapies not only utilize the host's immune response to combat disease …

Accelerate Vaccine Development Using Seamless Phase 2/3 Trial Designs, Jia-Ying Yang, Guo-Chun Li, Ying Yuan

Faculty, Staff and Student Publications

Background: Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines.

Research design and methods: This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, …

Mt-Keyboard: A Bayesian Model-Assisted Interval Design To Account For Toxicity Grades And Types For Phase I Trials, Kai Chen, Li Wang, Ying Yuan

Faculty, Staff and Student Publications

Conventionally, dose finding trials are based on dose-limiting toxicity (DLT) that only captures the most severe toxicities, e.g., treatment related grade 3 or higher toxicity according to the NCI Common Terminology Criteria for Adverse Events. However, this approach is often problematic for certain novel targeted therapies and immunotherapies, which may not induce DLT within a clinically active dose range and are often characterized by low grade toxicities. This important issue has been highlighted and discussed in the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forums, and is also an important consideration of the Project Optimus initiated by FDA to …

A Blood-Based Metabolite Signature For Personalized Risk Assessment Of Pancreatic Cancer, Ricardo A León-Letelier, Yihui Chen, Riccardo Ballaro, Ehsan Irajizad, Kim-An Do, Anirban Maitra, Jianjun Zhang, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

No abstract provided.

Circulating Tumor Dna (Ctdna) As A Biomarker Of Response To Therapy In Advanced Hepatocellular Carcinoma Treated With Nivolumab, Yehia I Mohamed, Sunyoung S Lee, Tarik Demir, Shadi Chamseddine, Zishuo Ian Hu, Lianchun Xiao, Khaled Elsayes, Jeffrey S Morris, Robert A Wolff, Rikita Hiatia, Aliya Qayyum, Asif Rashid, Dan G Duda, James C Yao, Michael Lapelusa, Eugene J Koay, Armeen Mahvash, Ahmed Al Azzam, Ecaterina E Dumbrava, Manal Hassan, Hesham M Amin, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Background: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).

Objective: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.

Methods: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.

Results: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had …

Plain Language Summary Of The Foenix-Cca2 Study: Futibatinib For People With Advanced Bile Duct Cancer, Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Juan W Valle, Chigusa Morizane, Thomas B Karasic, Thomas A Abrams, Junji Furuse, Robin Katie Kelley, Philippe A Cassier, Heinz-Josef Klümpen, Heung-Moon Chang, Li-Tzong Chen, Josep Tabernero, Do-Youn Oh, Amit Mahipal, Markus Moehler, Yoshito Komatsu, Daniel H Ahn, Robert S Epstein, Abdel-Baset Halim, Volker Wacheck, Yaohua He, Mei Liu, Karim A Benhadji, John A Bridgewater, Foenix-Cca2 Study Investigators

Faculty, Staff and Student Publications

What is this summary about?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their …

Lights And Shadows On Local Recurrence After Renal Surgery: When, Why And How To Manage, Luca Di Gianfrancesco, Alessandro Crestani, Antonio Amodeo, Paolo Corsi, Davide De Marchi, Eugenio Miglioranza, Giuliana Lista, Ferdinando Daniele Vitelli, Francesca Simonetti, Gian Maria Busetto, Ugo Giovanni Falagario, Martina Maggi, Filippo Marino, Giannicola Genovese, Roberto Falabella, Angelo Porreca

Faculty, Staff and Student Publications

Introduction: This review aims to analyze the existing literature on local recurrence (LR) in patients undergoing partial nephrectomy (PN) for renal cell carcinoma, identifying relative risk factors, and exploring optimal clinical management strategies.

Methods: A comprehensive literature search was conducted across bibliographic databases, primarily focusing on LR rates. Secondary outcomes included evaluation of positive surgical margins (PSM), nephrometry scores, pathological stage (T and grading), perioperative outcomes, time-to-LR, overall survival, and cancer-specific survival.

Results: Due to the heterogeneity, a narrative synthesis was performed. LR rates after PN varied in the literature; with PSM emerging as a significant risk factor. Other LR …

A Prospective Multi-Centered Registry-Based Observational Study For Patients With Cancer: Design And Rationale For Korean Medicine Cancer Registry (Kmcare), Jee Young Lee, Hayun Jin, Su Bin Park, Eun Hye Kim, Jee-Hyun Yoon, Seong Woo Yoon

Faculty, Staff and Student Publications

Background: Cancer is one of the leading causes of death in most countries with an expected increased burden on healthcare systems. Since integrative medical treatments are not collected within the scope of existing cancer registries, the establishment of the Korean Medicine Cancer Registry (KMCARE), gathering integrative therapies, including conservative care and Korean medicine, is warranted.

Methods: A prospective observational study based on the registry will be conducted in 5 Korean medical hospitals. A total of 650 eligible participants undergoing Korean medicine treatments within 1 month of a diagnosis of lung, colorectal, stomach, or breast cancer are anticipated to be enrolled …

Influence Of Oral Microbiome On Longitudinal Patterns Of Oral Mucositis Severity In Patients With Squamous Cell Carcinoma Of The Head And Neck, Liangliang Zhang, Erin Marie D San Valentin, Teny M John, Robert R Jenq, Kim-Anh Do, Ehab Y Hanna, Christine B Peterson, Cielito C Reyes-Gibby

Faculty, Staff and Student Publications

Background: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck.

Methods: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit …

Enhancing Efficacy Of The Mek Inhibitor Trametinib With Paclitaxel In Kras-Mutated Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid Powell, Yong Sung Park, Clifford Stephan, E Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Background: KRAS is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Objective: Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Design: In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that …

Enhanced Tumor Control And Survival In Preclinical Models With Adoptive Cell Therapy Preceded By Low-Dose Radiotherapy, Nahum Puebla-Osorio, Natalie Wall Fowlkes, Hampartsoum B Barsoumian, Kristina Xega, Gitika Srivastava, Claudia Kettlun-Leyton, Sara Nizzero, Tiffany Voss, Thomas S Riad, Christina Wong, Ailing Huang, Yun Hu, Joylise Mitchell, Mingee Kim, Zahid Rafiq, Kewen He, Duygu Sezen, Ethan Hsu, Fatemeh Masrorpour, Aurian Maleki, Carola Leuschner, Maria Angelica Cortez, Philipp Oertle, Marko Loparic, Marija Plodinec, Janet L Markman, James W Welsh

Faculty, Staff and Student Publications

Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone.

Methods: We investigated this hypothesis …

Postprogression Therapy And Confounding For The Estimated Treatment Effect On Overall Survival In Phase Iii Oncology Trials, Alexander D Sherry, Pavlos Msaouel, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Esther J Beck, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Eugene J Koay, Clifton David Fuller, Charles R Thomas, Zachary R Mccaw, Ethan B Ludmir

Faculty, Staff and Student Publications

Objective: Estimations of the treatment effect on overall survival (OS) may be influenced by post-progression therapies (PPTs). It is unclear how often OS analyses account for PPT effects. The purpose of this cross-sectional analysis was to determine the prevalence of OS analyses accounting for PPT effects in phase III oncology trials.

Methods and analysis: We screened two-arm, superiority design, phase III, randomised, oncology trials reporting OS from ClinicalTrials.gov. The primary outcome was the frequency of OS analyses adjusting for PPT confounding. Logistic regressions computed ORs for the association between trial-level covariates and the outcome.

Results: A total of 334 phase …