Medical Specialties Commons^™

Therapeutic Responses In Patients With Advanced Nsclc Enrolled In Early-Phase Clinical Trials At Md Anderson, Jeong Uk Lim, Heather Y Lin, Lei Kang, Hung Le, Tin-Yun Tang, Stephane Champiat, Ecaterina Elena Dumbrava, Xiuning Le, Aung Naing, Sarina A Piha-Paul, Jordi Rodon Ahnert, Apostolia Maria Tsimberidou, Timothy A Yap, Siqing Fu, Funda Meric-Bernstam, David S Hong

Faculty, Staff and Student Publications

We evaluated clinical outcomes and safety profiles in patients with non-small cell lung cancer (NSCLC) treated in early-phase trials. A retrospective review of 546 NSCLC cases treated from January 2016 to December 2024 at The University of Texas MD Anderson Cancer Center was performed using the MD Anderson CHIMERA database. Patients were categorized into seven groups based on treatment regimen. The overall objective response rate (ORR) was 19.9%, and the highest ORRs were in the targeted combination (30.8%) and targeted monotherapy (29.7%) groups. Gene alteration–matched therapy, serum albumin level, metastatic burden, treatment group, and liver metastasis were independently associated with …

Adipose Stromal Cell-Derived Cancer-Associated Fibroblasts Promote Pancreatic Adenocarcinoma Progression Through Sfrp4 Signaling, Joseph Rupert, Lingyi Cai, Alexes C Daquinag, Dimitris Anastassiou, Mikhail G Kolonin

Faculty, Staff and Student Publications

Background/objectives: Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis.

Methods: To explore the underlying molecular mechanisms, we used a model based on primary ASCs derived from human visceral adipose tissue co-cultured with human PDAC cell line Capan-1. To investigate cancer progression in vivo, we also used mice orthotopically grafted with mouse KPC cells.

Results: Genomic analysis revealed that Capan-1 co-culture induces Wnt and TGFβ signaling and extracellular matrix …

An Integrated Single-Cell And Spatial Transcriptomic Atlas Of Thyroid Cancer Progression Identifies Prognostic Fibroblast Subpopulations, Matthew A Loberg, George J Xu, Sheau-Chiann Chen, Hua-Chang Chen, Claudia C Wahoski, Kailey P Caroland, Megan L Tigue, Heather A Hartmann, Jean-Nicolas Gallant, Courtney J Phifer, Andres A Ocampo, Dayle K Wang, Reilly G Fankhauser, Kirti A Karunakaran, Chia-Chin Wu, Maxime Tarabichi, Sophia M Shaddy, James L Netterville, Sarah L Rohde, Carmen C Solórzano, Lindsay A Bischoff, Naira Baregamian, Barbara A Murphy, Jennifer H Choe, Jennifer R Wang, Eric C Huang, Quanhu Sheng, Luciane T Kagohara, Elizabeth M Jaffee, Ryan H Belcher, Ken S Lau, Fei Ye, Ethan Lee, Vivian L Weiss

Faculty, Staff and Student Publications

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts …

Precision Targeting Of Sting: Challenges, Innovations, And Clinical Outlook For Cancer Therapy, Jiaqi Shi, Yingying Zhang, Na Zhao, Ekihiro Seki, Li Ma, Gordana Kocic, Xiaobo Li, Janoš Terzić, Tongsen Zheng

Faculty, Staff and Student Publications

The stimulator of interferon genes (STING) pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy. Despite promising preclinical studies, clinical trials of STING agonists have largely failed to deliver durable efficacy, with no agents progressing to phase III trials. This review examines the biological, pharmacological, and clinical barriers limiting STING pathway activation in cancer treatment. We discuss the inherent limitations of STING agonists as well as host-related resistance driven by tumor heterogeneity, immune suppression, and chronic STING activation. Mechanisms of acquired resistance, such as immune checkpoint upregulation and suppression of effector …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

The Impact Of Nurse-Led Distraction Techniques On Pain And Anxiety During Cancer Treatment In Pediatric Oncology Patients: Examining Virtual Reality And Play Therapy, Alexis Abalos

Nursing | Senior Theses

Children undergoing cancer treatment often experience pain and anxiety during cancer treatment, including chemotherapeutic invasive procedures such as frequent port access or peripheral catheterization. Nurse-led distraction techniques, including virtual reality and play therapy, have emerged as promising non-pharmacologic interventions to reduce levels of pain and anxiety in pediatric oncology patients. This thesis analyzes existing data through a close examination of primary and secondary research articles that prove the effectiveness of virtual reality and play therapy on reducing pain, anxiety, and psychosocial distress in pediatric oncology patients receiving cancer treatment. Using the University of California, San Francisco (UCSF) Symptom Management Theory, …

The Nurse's Role In Curative-To-Palliative Transitions In Advanced Cancer: A Theory Synthesis Using Turner's Method, Geya George, Deborah Kirk, Davina Porock

Research outputs 2022 to 2026

Aim: This paper aims to explain the process of formulating a robust theory that comprehensively explains the nurse's role during the transition from curative to the palliative phase in advanced cancer care. Design: A qualitative theory synthesis approach was applied, utilising Turner's 9-step theory synthesis method to integrate five grounded theories and 10 qualitative studies. The Walker and Avant method of concept development and analysis further ensured rigour. Methods: Turner's theory synthesis was used to formulate a more comprehensive, testable theory from five existing grounded theories and 10 other qualitative studies that explain the nurse's role in supporting and facilitating …

Facilitators To The Implementation Of Exercise Into Cancer Care: A Systematic Review, Georgia L. White, Mary A. Kennedy, Brent J. Cunningham, Riley Dunn, Jason Martin, Meegan Walker, Craig T. Wallington-Gates, Hattie Wright, Bryan Chan, Grace L. Rose

Research outputs 2022 to 2026

Purpose: Although governing bodies urge the importance of integrating exercise into routine cancer care, facilitators to implementation have not been systematically identified and collated. This review aimed to summarise facilitators to implement exercise services within real-world settings. Methods: A systematic review of qualitative, quantitative, and mixed-method studies was conducted (three databases, 13th September 2024). Reports were included if they documented the implementation of co-located exercise services (delivered onsite within cancer centres) or referral pathways to external exercise services from cancer centres. The updated Consolidated Framework for Implementation Research (CFIR 2.0) was used to code and synthesise facilitators. Results: Of 8544 …

Priorities For Multimorbidity Management And Research In Cancer: A Delphi Study Of Australian Cancer Survivors, Clinicians, And Researchers, Rebecca L. Venchiarutti, Haryana Dhillon, Carolyn Ee, Nicolas H. Hart, Michael Jefford, Bogda Koczwara

Research outputs 2022 to 2026

Purpose: Multimorbidity is common in people with cancer and associated with increased complexity of care, symptoms, mortality, and costs. This study aimed to identify priorities for care and research for cancer survivors with multimorbidity. Methods: A Delphi consensus process was conducted. Elements of care and research were based on Australia’s National Strategic Framework for Chronic Conditions, a literature review, and expert input. In Round 1, health professionals, cancer survivors, and researchers rated the importance of 18 principles, 9 enablers, and 4 objectives. In Round 2, new elements were rated and all elements were ranked. Results: In Round 1, all elements …

Nanosecond Electric Pulses As A Novel In Situ Vaccination Strategy For Cancer Treatment: Mechanisms, Challenges And Prospects, Siqi Guo

Bioelectrics Publications

Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation approach due to their high spatial precision, preservation of critical tissue structures, and minimal adverse effects. One of the most significant discoveries associated with nsEP tumor ablation is the induction of potent systemic antitumor immunity, particularly in situ vaccination (ISV) effects and, in some cases, abscopal effects against distant untreated tumors. Substantial evidence demonstrates that nsEPs can …

Insidious Abdominal Pain Masked By Kratom Abuse; A Case Of Lynch Syndrome, Grant Read, Khloe Gu, Jessica Klingensmith, Ameet Patel

West Florida Division GME Research Day 2026

No abstract provided.

A Review Of Mobility And Gait Changes In Patients With Prostate Cancer: Disease Stage, Symptom, And Treatment-Related Influences, Lauren Hathorn, Abigail Schmitt Dr

2026 Honors Symposium

Background: This review examines the impact of prostate cancer symptoms, progression, and treatments on patients’ gait and mobility. Prostate cancer is the leading cancer diagnosis for men in the United States, with an increase in incidents in the last decade. Prostate cancer, its progression, and its various symptoms and treatments have both physical and functional consequences that often cause changes in patients’ mobility and gait. Some studies have found gait to be a predictor of functional decline and mortality. Given that functional decline and mortality are also consequences of cancer progression and cancer treatments, gait analysis could offer a non-invasive …

From Screens To Stress: Public Health Implications Of Cancer Worry In A Digitally Connected World, Shreya Mathur, Ethan Burns, Michael Pokojovy, Tzu-Liang Bill Tseng, Sunil Mathur

Mathematics & Statistics Faculty Publications

Aims:

This study examines how digital information environments, genetic testing experiences, health behaviors, and psychological distress influence cancer-related worry among adults in the United States. It further considers the public health implications of elevated or reduced cancer worry for prevention and risk communication.

Methods:

Data were drawn from a nationally representative survey of 6,252 U.S. adults. Measures included reliance on social media for health decision-making, smoking status, history of genetic testing, and psychological distress. Multivariable analyses assessed associations between these factors and levels of cancer worry.

Results/Findings:

Reliance on social media for health decisions was associated with greater cancer worry, …

Implementing A Standardized App-Led Multidisciplinary Medication Review And Reconciliation To Improve Medication Safety Before Systemic Cancer Therapy: An Ambulatory Oncology Quality Improvement Initiative, Sarah R. Hines

DNP Projects

Background

Adult patients initiating systemic cancer therapy frequently present with pre-existing polypharmacy related to chronic comorbidities and cancer-related symptom management. The addition of anticancer therapies and supportive care medications further increases medication burden and the risk of medication-related harm. Although national organizations and institutional policies recommend comprehensive medication review before treatment initiation, implementation remains inconsistent in ambulatory oncology practice.

Purpose

To implement and evaluate a standardized Advanced Practice Provider (APP)-led multidisciplinary medication review and reconciliation process designed to identify medication medication-related safety risks before initiation of systemic cancer therapy in adult oncology patients receiving care in an ambulatory infusion center. …

Clinical Outcomes With Perioperative Nivolumab By Nodal Status In Patients With Stage Iii Resectable Nsclc: Phase 3 Checkmate 77t Exploratory Analysis, Mariano Provencio, Mark M Awad, Jonathan D Spicer, Annelies Janssens, Fedor Moiseyenko, Yang Gao, Yasutaka Watanabe, Aurelia Alexandru, Florian Guisier, Nikolaj Frost, Fabio Franke, T Jeroen Nicolaas Hiltermann, Jie He, Fumihiro Tanaka, Shun Lu, Cinthya Coronado Erdmann, Padma Sathyanarayana, Phuong Tran, Vipul Devas, Tina Cascone

Faculty, Staff and Student Publications

Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30–0.70)) and pathological complete response rate …

Persistent Racial And Sex-Based Disparities In Radiation Receipt And Survival Among Patients With Anal Cancer, Yashaswi Koguru, Austin Mccrea, Stephen Meyer

South Atlantic Division GME Research Days 2026

No abstract provided.

Spontaneous Hemidiaphragm Elevation, A Subtle, Early Sign Of Malignancy, Michael Lee Phillips, Caitlyn Brown, Rena Phillips, John Ashby, Chad Martins

South Atlantic Division GME Research Days 2026

No abstract provided.

An Analysis Of Heart Failure Among Cancer Patients In The United States Between 1999 And 2020, Abes A. Bautista Neughebauer, Deepak Talreja, Apostolos Gaitanidis

Department of Medicine Faculty Publications

Background: Cancer and heart failure (HF) are highly prevalent in the population and can co-exist, due to shared risk factors and an aging population. The HF-related mortality burden in cancer patients across in the United States (US) remains poorly understood. The goal of this study is to evaluate the patterns of HF-related deaths among cancer patients in the United States.

Methods: A retrospective analysis was performed using the Centers for Disease Control and Prevention (CDC) WONDER Multiple Cause of Death database between years 1999 and 2020. HF-related deaths were defined as death certificates listing HF as a contributing cause of …

Perspective: Radiotherapy And Body Composition: Unmet Needs In Low- And Middle-Income Countries, Alexia J Murphy-Alford, Aaron J Grossberg, Vickie E Baracos, Maha Barbar, Judy Bauer, Jonathan P Bennett, Elena Fidarova, Clifton D Fuller, Anastassia Löser, Amy C Moreno, Anurima Patra, Deepa Puttaswamy, David I Rosenthal, Judy Schoeman, Yavuz Anacak

Faculty, Staff and Student Publications

Radiotherapy plays a vital role in cancer treatment, yet its effects on patients' nutritional status can precipitate muscle loss, with significant implications for treatment tolerance and outcomes. Evidence from high-income countries increasingly links radiation-induced muscle loss to adverse clinical outcomes. In contrast, low- and middle-income countries face a stark evidence gap, despite the heightened vulnerability of cancer patients in these settings due to delayed diagnosis, limited access to care, and high rates of co-morbidities. This paper highlights the critical gaps in nutritional care for radiotherapy patients in low- and middle-income countries.

Intratumoral Bacteria Are Immunosuppressive And Promote Immunotherapy Resistance In Head And Neck Squamous Cell Carcinoma, Natalie L Silver, Jin Dai, Travis D Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J H Shih, Shwetha V Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G Sikora, Elias J Sayour, Apollo Stacy, Christian Jobin, Timothy A Chan, Renata Ferrarotto, Daniel J Mcgrail

Faculty, Staff and Student Publications

Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation …

Using A Heuristic Tool To Improve Symptom Self-Management In Adolescents And Young Adults With Cancer: Protocol For A Randomized Controlled Trial., Suzanne Ameringer, Grace Hodges, R K Elswick, Lauri Linder, Catherine Fiona Macpherson, Kristin Stegenga

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adolescents and young adults (AYAs) with cancer experience multiple distressing symptoms during treatment, yet few developmentally relevant resources have been developed to help them self-manage their symptoms. Empowering patients to have a more active role in self-management during cancer treatment may lessen their symptom severity and distress.

OBJECTIVE: The aim of this study is to test an intervention designed to improve symptom self-management, the Computerized Symptom Capture Tool (C-SCAT), by helping AYAs understand their unique symptom experience and discuss it with their health care providers.

METHODS: We are conducting a multisite, 2-group randomized controlled trial to evaluate the effects …

Protocol For Isolation Of Lipid Droplets And Mitochondria From Acute Myeloid Leukemia Cells For Lipidomic Analysis, Ran Zhao, Liang Zhang, Shuxin Dong, Kazuharu Kamachi, Saurabh Kumar Gupta, Hiroki Akiyama, Jalen Nguyen, G Lavender Hackman, Michael Andreeff, Alessia Lodi, Jo Ishizawa

Faculty, Staff and Student Publications

Lipid droplets (LDs) are dynamic organelles critical for lipid and energy homeostasis. LD dysregulation is implicated in various diseases, including acute myeloid leukemia (AML), which exhibits aberrant lipid metabolism and chemoresistance. Here, we describe an effective protocol for the co-isolation of LDs and mitochondria from lipid-deficient cell types, e.g., AML cells. We detail procedures for the isolation, quality verification, and results from mass spectrometry-based lipidomic analysis. This protocol enables the functional study of organellar lipidomic regulation in AML.

Measurable Imaging-Based Changes In Enhancement Of Intrahepatic Cholangiocarcinoma After Radiotherapy Reflect Physical Mechanisms Of Response, Brian De, Prashant Dogra, Mohamed Zaid, Dalia Elganainy, Kevin Sun, Ahmed M Amer, Charles Wang, Michael K Rooney, Enoch Chang, Hyunseon C Kang, Zhihui Wang, Priya Bhosale, Bruno C Odisio, Timothy E Newhook, Ching-Wei D Tzeng, Hop S Tran Cao, Yun S Chun, Jean-Nicholas Vauthey, Sunyoung S Lee, Ahmed Kaseb, Kanwal Raghav, Milind Javle, Bruce D Minsky, Sonal S Noticewala, Emma B Holliday, Grace L Smith, Albert C Koong, Prajnan Das, Vittorio Cristini, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

Escalated doses of radiotherapy associate with improved local control and overall survival (OS) in intrahepatic cholangiocarcinoma (iCCA), but personalization remains limited because conventional size-based CT criteria correlate poorly with outcomes. We hypothesized that quantitative enhancement measurements would better predict clinical outcomes and guide individualized RT optimization. In a retrospective cohort of 154 patients, we analyzed pre- and post-RT CT scans using quantitative European Association for Study of Liver (qEASL) to derive viable tumor volumes, comparing enhancement-based metrics with size-based RECIST and linking them to outcomes via survival and mathematical modeling. Change in enhancement volume was strongly associated with OS after …

Stromal Fibroblastic Mutant Trp53 Promotes Mammary Tumor Development Via Enhanced Secretion Of Paracrine Factors, Bin Liu, Shunbin Xiong, Abie Williams-Villalobo, Gilda Chau, Yuan Qi, Hehua Chen, Carenza Johnson, Dhruv Chachad, Joy Mcdaniel, Xiaoping Su, Adel K El-Naggar, Guillermina Lozano, Yun Zhang

Faculty, Staff and Student Publications

Mutations in the tumor suppressor gene TP53 have been identified in breast cancer-associated fibroblasts and are associated with poor patient prognosis. However, the functional impact of fibroblastic mutant p53 on breast cancer development remains unclear. To investigate this, we compared female mice harboring HER2-driven mammary tumors with a fibroblast-specific Trp53 mutation (NP) to those with wild-type fibroblastic Trp53 (N). NP mice exhibited significantly shorter median tumor-free survival than N mice. RNA sequencing of NP and N tumors and mammary glands revealed numerous differentially expressed genes (DEGs) between tumors and the corresponding glands in both genotypes. Notably, the NP tumors showed …

Structural Birth Defects And Leukemia Risk In Children With Down Syndrome, Ching-Ju Hsu, Jeremy M Schraw, Sonja A Rasmussen, Tiffany M Chambers, Tania A Desrosiers, Chad D Huff, Amanda E Janitz, Russell S Kirby, Eirini Nestoridi, Wendy N Nembhard, Jason L Salemi, Charles Shumate, Jean Paul Tanner, Mahsa M Yazdy, Michael E Scheurer, Karen R Rabin, Philip J Lupo

Faculty, Staff and Students Publications

Birth defects are associated with increased cancer risk in the general pediatric population, yet their impact on leukemia risk in children with Down syndrome (DS) remains uncertain. We assessed this using data from 26,660 children with DS in the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study. Among them, 71.9% had at least one major birth defect, predominantly involving the cardiac (64.2%), musculoskeletal (21%), and gastrointestinal systems (6.8%). The cumulative incidence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) was comparable in children with and without co-occurring defects. Adjusted hazard ratios (aHR) for ALL and …

Racial And Ethnic Disparities In Neoadjuvant Chemotherapy Patterns And Outcomes In Early-Stage Her2-Positive Breast Cancer, Inimfon Jackson, Xiudong Lei, Hui Zhao, Rashmi Murthy, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

We examined neoadjuvant chemotherapy (NACT) use, pathological complete response (pCR) and the association with overall survival (OS) among patients with early-stage HER2-positive breast cancer (BC). Patients ≥18 years with stage I-III HER2-positive BC from 2010-2022 who had surgery and chemotherapy were identified. Of 195,023 patients treated with chemotherapy, 37.7% received NACT. NACT use increased from 18.6% in 2010 to 63.4% in 2022 (p <  0.001) and pCR rates rose from 21% to 47.6% (p <  0.001). Black patients were less likely to receive NACT (aOR = 0.96;95%CI 0.93-0.99) or achieve pCR (aOR = 0.86;95%CI 0.82-0.90) than White patients. pCR was associated with a reduction in the risk of death (aHR = 0.45;95%CI 0.42-0.48). 3-year OS increased from 91% in 2010 to 95% in 2019 for patients without a pCR (p <  0.001), and from 97% to 99% for patients with pCR (p = 0.002). Further research is needed to understand and address racial and ethnic disparities in treatment access and outcomes.

Cdk2 Inhibition Enhances Cdk4/6 Inhibitor Antitumor Activity In Comprehensive Breast Cancer Pdx Model Screen, Nealia C House, Maxine M Chen, Sima Khazaei, Victoria Brown, Philip Ramsden, David H Peng, Sydney Moore, Liang Yuan, Rentian Wu, Fangyang Wang, Linjie Luo, Ningping Feng, Christopher A Bristow, Timothy A Yap, Khandan Keyomarsi, Joseph R Marszalek, Scott Ribich, Mikael L Rinne, Lakshmi B Muthuswamy, Kerrie L Faia

Faculty, Staff and Student Publications

Aberrant cyclin-dependent kinase 2 (CDK2) activity is implicated as a resistance mechanism to CDK4/6 inhibitors (CDK4/6i) in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Using preclinical patient-derived xenograft models, the CDK2i + CDK4/6i combination was active broadly across CDK4/6i-resistant and -naïve HR+ and triple-negative breast cancer models. A novel, weighted mRNA expression signature involving CCND1, CCNE1, RB1, and CDKN2A (p16) predicted response to combined inhibition of CDK2 and CDK4/6. Addition of endocrine therapy significantly enhanced antitumor activity in HR+ models, providing preclinical proof-of-concept for the broad antitumor activity of the triple combination. Early clinical data demonstrated …

Predicting The Response Of Triple Negative Breast Cancer To Neoadjuvant Systemic Therapy Via Biology-Based Modeling And Habitat Analysis, Casey E Stowers, Chengyue Wu, Clinton Yam, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite being the standard-of-care treatment, neoadjuvant therapy (NAT) attains a complete response only in approximately half of the patients with triple negative breast cancer. Thus, methods to predict and optimize patient response to NAT are needed. Previously, we employed patient-specific MRI data to calibrate a biology-based mathematical model that describes cell movement, proliferation, and death due to drug at the tumor level and cell proliferation at an image voxel level. We now extend our approach by using MRI data to group voxels into "habitats" whereby tumor cells of a habitat share the same proliferation. With this approach, we now calibrate …

Diras3-Derived Cyclic Peptides Disrupt Kras-Raf Interaction And Kras Nanoclustering, Suppressing Kras-Driven Pancreatic And Ovarian Tumors, Joshua P Gray, Gamze Bildik, Ha-Neul Kim, Margie N Sutton, Jing Wang, Amarachi O Osuji, Nefeli Batistatou, Hailing Yang, Weiqun Mao, Zhi Tan, Geneviève M C Gasmi-Seabrook, Junchen Liu, John F Hancock, Christopher B Marshall, Joshua A Kritzer, Mitsuhiko Ikura, Robert C Bast, Steven W Millward, Zhen Lu

Faculty, Staff and Students Publications

Mutations in KRAS drive 88% of pancreatic ductal adenocarcinomas (PDAC) and up to 40% of low-grade serous ovarian cancers (LGSOC), making KRAS a long-standing therapeutic target. We previously showed that DIRAS3 binds RAS, forming heterodimers that disrupt RAS clustering and downstream MAPK signaling. Building on this, we developed conformationally constrained DIRAS3-derived peptides using two cyclization strategies and characterized them by NMR and biolayer interferometry. These cyclic peptides attenuate the interaction between KRAS and the BRAF RAS-binding domain, penetrate cells efficiently, and inhibit KRAS nanoclustering on the inner leaflet of the plasma membrane. Functionally, they reduce cell viability and suppress PDAC …

Shp2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy To Cancer Treatment And Vascular Risk, Silvia Fernanda López Moreno, Stefania Assunto Lenz, Bernardo Casso-Chapa, Angelica Paniagua-Bojorges, Jung Hyun Kim, Nicolas L Palaskas, Kevin T Nead, Venkata S K Samanthapudi, Gilbert Mejia, Oanh Hoang, Jonghae Lee, Steven H Lin, Joerg Herrmann, Guangyu Wang, Syed Wamique Yusuf, Cezar A Iliescu, Noah I Beinart, Charlotte Manisty, Masuko Ushio-Fukai, Tohru Fukai, Pietro Ameri, Roza I Nurieva, Michelle A T Hildebrandt, Keri Schadler, Efstratios Koutroumpakis, Sivareddy Kotla, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Student Publications

Src homology 2-domain containing protein tyrosine phosphatase 2 (SHP2), encoded by the Ptpn11 gene (Tyrosine-protein phosphatase non-receptor type 11), is a key downstream effector of PD-1/PD-L1 signaling and is likely important, in addition to immune modulation, in tumor development and vascular homeostasis. SHP2 conveys PD-1 mediated inhibitory signaling in T cells, and is emerging as a therapeutic target. Importantly, there is an association between immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs), and cardiovascular complications, underscoring the need to understand SHP2’s role in these processes. This review aims to summarize current knowledge on SHP2/PTPN11 biology, its role in immune …