Medical Specialties Commons^™

Improving Access To Specialized Rare Cancer Care Through A Navigation-Driven Centralized Metastatic Uveal Melanoma Multidisciplinary Tumor Board, Jameson Lynch, Rn

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Background

Metastatic uveal melanoma (mUM) is a rare malignancy; up to 50% of patients with uveal melanoma develop systemic metastases, with liver involvement occurring in up to 90% of metastatic cases.1 Thomas Jefferson University Hospital has extensive experience managing liver-dominant mUM, supported by prior single-institution longitudinal data involving 730 patients with uveal melanoma liver metastasis.3 This mUM program represents a specialized referral model for complex liver-dominant disease, offering multidisciplinary review, advanced liver-directed treatment planning, and coordinated access to specialty oncology care. Oncology navigation facilitates this model by coordinating intake, acquisition of outside imaging and records, pre-travel case preparation, tumor board …

Deaths Of Despair Among Cancer Survivors In Rural/Urban Appalachia (2000-2022), Jason Semprini, Anders Erickson, Nosa Osazuwa-Peters

Journal of Appalachian Health

Introduction: Rising deaths of despair (premature deaths from suicide, overdose, alcohol, and violence) in adults under age 65 persist across the United States, especially in Appalachia. People diagnosed with cancer may face elevated risks of such deaths due to pain, psychosocial distress, and financial hardship.

Purpose: Deaths of despair trends were compared among adults with cancer across Appalachian and non-Appalachian regions, stratified by sex and rurality.

Methods: Analyzing SEER-21 Incidence-Based Mortality data (2000–2022), deaths caused by suicide, cirrhosis of the liver, or accidents (includes overdose) were identified among adults aged 20–64 years. Annual mortality rates per 100,000 total population were …

Early-Onset Colorectal Cancer With Liver-Only Metastases: A Retrospective Cohort Study Integrating Prospectively Collected Real-World Clinical And Molecular Data From An Australian National Database (2009–2024) To Guide Treatment Planning, Savio G. Barreto, Christos S. Karapetis, Shahid Ullah, Matthew Burge, Susan Caird, Angus Campbell, Azim Jalali, Ross Jennens, Muhammad A. Khattak, Belinda Lee, Stephanie H. Lim, Shehara Mendis, Louise Nott, Timothy J. Price, Jeremy D. Shapiro, Jeanne Tie, Javier Torres, Colin Williams, Rachel Wong, Vanessa Wong, Peter Gibbs

Research outputs 2022 to 2026

Objective: To leverage the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (an Australian cancer database) to explore the ideal timing and sequence of therapies and the factors influencing these decisions in colorectal cancer (CRC) patients with liver-only metastases to inform contemporary decision-making and future trials.

Study Type: Retrospective registry-based cohort study using the TRACC registry.

Setting and Participants: Consecutive patients with liver-only metastatic CRC enrolled in the TRACC registry.

Main Outcome Measures: To explore cancer biology, intended treatment at presentation, actual treatment received and the resultant outcomes for early-onset CRC (EOCRC) (≤ 50 years) and late-onset CRC (LOCRC) …

Exploring Caregiving Choice In The Adult Cancer Population, Jennifer L. Huggins

MUSC Theses and Dissertations

ABSTRACT Purpose Although extensive research examines family caregivers (FCs) across populations, less attention has been paid to how lack of choice in assuming the role affects quality of life (QOL) among FCs of adults with cancer. Understanding choice could guide interventions protecting this invaluable, often invisible workforce. Aims (1) Synthesize what is known about perceived choice among informal caregivers of adults with serious illness; (2) assess relationships between caregiving choice and caregiver QOL, burden, sleep, depression, stress, and social determinants of health; (3) describe experiences of FCs of adults with cancer providing care with no, little, or some choice. Design …

Muscle–Tumor Crosstalk In Exercise Oncology: Exercise-Induced Myokines And Cancer Cachexia, Amirhossein Ahmadi Hekmatikar, Francesco Bettariga, Álvaro López Llorente, Diego Fernández-Lázaro, Katsuhiko Suzuki, D. Maryama Awang Daud

Research outputs 2022 to 2026

Exercise-induced myokines, such as IL-6, irisin, and myostatin, play crucial roles in mediating systemic adaptations and modulating tumor progression. This narrative review synthesizes evidence on how regular moderate-intensity exercise affects the myokine network within the tumor microenvironment (TME) of solid tumors. Results from the 86 included studies indicate that structured training (aerobic: 45–65% VO2 max; resistance: 45–70% 1RM) enhances the expression of beneficial myokines that support immune surveillance, reduce inflammation, and improve muscle–tumor cross-talk. IL-6 demonstrates a dual modulatory effect on inflammation and immunity; irisin contributes to tumor apoptosis, while myostatin downregulation supports muscle integrity and metabolic balance. Evidence suggests …

Detection, Persistence, And Rising Prevalence Of Oncogenic Viruses Revealed By Wastewater Metagenomics, Michael Tisza, Sara J Javornik Cregeen, Jennifer Deegan, Joseph F Petrosino, Eric Boerwinkle, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Oncogenic viruses cause high-risk cancers in humans and are responsible for nearly 20% of all cancer cases worldwide. Currently, very limited data exist in the realm of wastewater-based viral epidemiology (WBE) for cancer-causing viruses, with existing studies using targeted approaches (i.e., PCR-based approaches) that lack genomic resolution. In this study, we used a hybrid-capture approach to detect, filter, and sequence all known oncogenic virus signals from wastewater samples collected over 3 years (May 2022-May 2025) in 16 Texas cities, covering nearly 25% of the state's population. Once sequenced, we used custom computational tools designed for wastewater metagenomics to assign reads …

Histone Deacetylase Enzyme Activity Is Not The Universal Anticancer Target Of Hdac Inhibitors, Wenbo Li, Hyun-Hwan Jeong, Chengchuang Song, Panpan Liu, Yingjie Chang, Hao Fang, Udhaya Kumar S, Yuxiang Sun, M James You, Dongyin Guan, Zhandong Liu, Leng Han, Xuben Hou, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase inhibitors (HDIs) are approved for treating hematologic cancers and are currently being evaluated in hundreds of clinical trials for various cancers and other diseases, although their mechanisms of action remain poorly understood. Here, our unbiased bioinformatics analyses found that, for most cancer types, expression levels or genetic variants of histone deacetylase (HDACs) do not consistently correlate with carcinogenesis, do not predict cancer patient survival, and do not associate with cellular responses to HDIs. Whole-genome CRISPR library screens did not identify HDACs as genes affecting cellular responses to HDIs. Overexpression of dominant-negative Class I HDACs causes similar protein hyperacetylation …

Integrated Proteogenomic And Metabolomic Profiling Of Acute Myeloid Leukemias To Identify Molecular Subtypes And Associated Therapy Targets, Jennifer E Kyle, Raghav Jain, Yamei Deng, Marina A Gritsenko, Leanne E Henry, Jonathan T Lei, Yongchao Dou, Bahar Tercan, Zhiao Shi, Mahnoor N Gondal, Chia-Feng Tsai, John M Elizarraras, Rosalie K Chu, Fengchao Yu, Sunil K Joshi, Xiaojun Jing, Daniel A Polasky, Karl K Weitz, Ginny Xiaohe Li, Vanessa L Paurus, Chaevien S Clendinen, Athena A Schepmoes, Priscila M Lalli, Josie G Eder, Javier E Flores, Kelly G Stratton, James C Pino, Camilo Posso, Vladislav A Petyuk, Tyler J Sagendorf, Yuanwei Xu, Omar M Ibrahim, Ronald J Moore, Rui Zhao, Jin Chen, Matthew E Monroe, Mathangi Thiagarajan, Galen Hostetter, Chelsea Newton, Eunkyung An, Ana I Robles, Xu Zhang, Nathan J Edwards, Yin Lu, Hui Zhang, Haitham Abdelhakim, Paul D Piehowski, Mehdi Mesri, Richard D Smith, Chandan Kumar-Sinha, Cristina E Tognon, Jennifer Dunlap, Elie Traer, Li Ding, Jeffrey W Tyner, Arul M Chinnaiyan, Gilbert S Omenn, Karin D Rodland, Saravana M Dhanasekaran, Sara J C Gosline, Alexey I Nesvizhiskii, Bing Zhang, Tao Liu, Marcin P Cieslik, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematological malignancy. Here, to better define this clinically taxing and translationally challenging malignancy, we applied a multiomics approach, consisting of 13 modalities to analyze 173 treatment-naive individuals with AML. By integrating these 'omes', we identified distinct AML subtypes, genotype-phenotype associations, biomarkers and pathobiological mechanisms. Across the spectrum of primitive and committed AML, we found extensive metabolomic and lipidomic reprogramming driven by divergent MYC and mTOR activity. We linked metabolic changes to striking hyperacetylation of mitochondrial proteins in CEBPA-mutant AML. Protein-centric subtyping revealed a distinct NPM1-mutant subset characterized by outlier expression …

Associations Between Neighborhood Disadvantage, Cannabis Use, And Patient-Reported Outcomes Among Patients With Cancer, Brittney Greene, Shilpa Ghosh, Craig Colder, Salimah Meghani, Brooke Worster, Rebecca Ashare

Kimmel Cancer Center Faculty Papers

INTRODUCTION: Cannabis use is proliferating among oncological populations. However, research is limited on whether cannabis routes and sources are associated with neighborhood disadvantage and whether it moderates the relationship between neighborhood disadvantage and patient-reported outcomes (PROs). This analysis evaluates the relationship between neighborhood disadvantage and cannabis source and route, and their association with PROs.

METHODS: Analyses included 106 patients with cancer from varying levels of neighborhood disadvantage. Logistic regressions tested the association of neighborhood disadvantage with cannabis source (i.e., regulated vs. unregulated) and route (i.e., inhaled vs. consumed/other formulations). Multilevel regressions tested the association of neighborhood disadvantage with PROs (e.g., …

Cardiac Hdac3 Disruption Contributes To Hdac Inhibitor-Induced Qt Prolongation, Lilei Zhang, Jiang Chang, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, …

Transitioning To Adolescent And Young Adult Or Adult Cancer Survivorship Care: A Systematic Review Of Contemporary Guidelines And Trials, Darren Haywood, Hammersley, Ursula Sansom-Daly, Jordana Mcloone, Evan Dauer, Helen Wilding, Nicolas H. Hart, Thomas Walwyn

Research outputs 2022 to 2026

Background: Health service transitions of child, adolescent, and young adult cancer survivors between paediatric and adult cancer care services are pervasively fragmented, resulting in poor coordination, reduced satisfaction, and adverse outcomes for cancer survivors and significant others (e.g., caregivers and family members). Numerous trials and clinical guidelines have been developed to support care transitions, but their convergence, divergence, and methodological quality remain unclear. To advance clinical practice and quality research about care transitions, a synthesis of trials and guidelines on child, adolescent, and young adult care transition across age-appropriate cancer services is required to inform future research, practice, guideline, and …

A Systematic Review And Meta-Analysis On The Levels Of Supportive Care Needs In Adults With Cancer, Caroline B. Silveira, Rech, Maria Petropoulou, Pietro S. Rössler, Francine F. De Souza, Helena B. Böhmer, Amanda L. Giacomet, Richard Alejandro B. De Barros, Lucélia De C. De Barros, Vagner R.Z.B. Pereira, Nanci Da S.T. Junqueira, Pedro Lopez

Research outputs 2022 to 2026

Objective: To estimate the levels of supportive care needs among adults with cancer using the Supportive Care Needs Survey–Short Form 34 (SCNS-SF34) and to examine demographic, clinical, and treatment-related determinants. Methods: A systematic review and meta-analysis was conducted (CRD42024604977). Studies reporting SCNS-SF34 scores in adults with cancer were included. Searches were performed across six different databases (November 2024; updated August 2025). Random-effects meta-analyses were undertaken to estimate the pooled mean scores across the five SCNS-SF34 domains and total score. Subgroup and meta-regression analyses explored potential determinants. Results: Ninety-five studies (n = 32,493) were analysed. The unmet needs observed tended to …

Technical Development, Optimization, And Clinical Implementation Of Quantitative Magnetic Resonance Imaging Methods For Radiation Oncology, Lucas Mccullum

Dissertations and Theses (Open Access)

Magnetic resonance imaging (MRI) has gradually grown more important in the field of radiation oncology. This paradigm shift has grown from initial experiments with MRI of cancerous lesions in the early 1970s, to the integration of MRI images for radiation therapy treatment planning (i.e., MRI-Simulation) in the early 1980s, to the combined MRI linear accelerator (MR-Linac) becoming commercially available in 2018 which can simultaneously image a tumor and treat it with radiation. However, due to its novelty in radiation oncology, its full potential for the integration of quantitative MRI-based biomarkers has yet to be fully realized.

Therefore, this dissertation will …

Emerging Nanotherapy Applications In Cancer Treatment: A Comprehensive Review, Waleed H. Mahallawi

Saudi Medical Journal

This comprehensive review synthesizes recent advances in cancer nanotherapy, focusing on 6 emerging categories: immunomodulation, gene/RNA delivery, theranostics, radiosensitization, biomimetic carriers, and artificial intelligence (AI)-guided formulations. These innovative platforms demonstrate transformative potential by overcoming key limitations of conventional cancer treatments. Immunomodulatory nanoparticles reprogram tumor microenvironments and convert immunologically ``cold'' tumors to ``hot'' responsive states. Gene delivery systems enable precise editing with >50% efficiency, while theranostic platforms integrate real-time imaging with targeted therapy. Radiosensitizers amplify local radiation dose by twofold, and biomimetic carriers achieve prolonged circulation through immune evasion. An AI-driven approaches optimize personalized formulations based on patient-specific biomarkers. Clinical evidence …

Lessons Learned For Improving Trainee Engagement And Utilization Of Education And Training Materials For Cancer Research, Katerina M. Santiago, Tania Galindo, Michaela A. Dinan

Advances in Cancer Education and Quality Improvement

Background: A core component of the National Cancer Institute Cancer (NCI) Cancer Center Support Grant requires cancer centers to coordinate research career enhancement and related activities. The Yale Cancer Center, an NCI-designated comprehensive cancer center, established the Cancer Research Training and Education Coordination (CRTEC) component in 2016. In response to the needs of trainees, CRTEC has developed several initiatives that we have identified and described here as best practices to engage and support trainees.

Methods: We had 2 aims to improve engagement: 1) increasing our visibility and trainee awareness of CRTEC and nurturing bidirectional communication and 2) offering …

Tom: Treatment Outcome Monitor - A Web-Based Tool Designed Specifically For Clinics With Limited Resources, Saurabh Shashikumar Nair, Alba Kihn Alarcon, Maritza Elodia Cupil Barrios, Milton Estuardo Ixquiac Cabrera, Mynor Villeda, Joseph Steyn, Anneray Richards, Ricardo Ruggeri, Loida Orozco, Angel Velarde, Indranil Mallick, Graeme Lazarus, Christoph Trauernicht, Vicky De Falla, Tim Edwards, Johnny Inthaphone, Adenike Olanrewaju, Laurence E. Court, Joshua Niedzielski

Advances in Cancer Education and Quality Improvement

Background: Although three-fourths of cancer deaths are expected to occur in low- and middle-income countries (LMICs) by 2030, most cancer research still comes from high-income countries. One barrier to cancer research in LMICs is lack of infrastructure for systematic data collection, including electronic medical record systems. We developed Treatment Outcome Monitor (TOM), a cloud-based tool for tracking cancer patient outcomes, designed specifically for resource-limited settings.

Methods: TOM was developed through iterative design cycles with continuous feedback from health care providers from across the world. We focused on creating a simple, web-based solution that addresses real-world challenges in resource-limited …

Progesterone Receptors Drive Advanced Breast Cancer Phenotypes Including Circulating Tumor- And Stem-Like Cell Expansion In The Context Of Esr1 Mutation, Thu H. Truong, Noelle E. Gillis, Amy R. Dwyer, Rosemary J. Huggins, Kyla M. Hagen, Sai Harshita Posani, Nuri A. Temiz, Carlos Perez Kerkvliet, Ellie M. Piepgras, Julie H. Ostrander, Geoffrey L. Greene, Carol A. Lange

Department of Urology Faculty Papers

Endocrine therapy resistance remains a major challenge in the treatment of advanced estrogen receptor positive (ER+) breast cancer. This can be driven by acquired mutations in the estrogen receptor gene (ESR1), such as Y537S or D538G, that results in constitutive estrogen-independent ER activity. Progesterone receptors (PR) are important modifiers of ER activity, in part via direct binding. We previously showed that PR mediates expansion of cancer stem-like cell (CSC) populations. In this study, we sought to define whether PR function changes in the context of ESR1 mutations. PR readily interacted with wild type (WT), but not Y537S or D538G ERs. …

Evaluating The Effects Of Akt Knockdown And Everolimus Treatment On Ewing Sarcoma, Arisha Arif, Alfie Barcenez, Nicole Vanegas-Riddick

Posters - 2026

The purpose of this study is to use the gene AKT1, due to the interest in AKT1’s role in cancer cell proliferation, and the drug Everolimus, to determine if combined targeted therapy works as a more efficient therapeutic approach. We hypothesize that the knockdown of AKT1 will increase the sensitivity of Ewing sarcoma cells to Everolimus, resulting in reduced proliferation and/or survival compared to drug treatment alone. This would suggest that AKT1 normally protects cells from drug-induced stress. Ewing Sarcoma has been connected to chromosomal translocations and most common in pediatric patients. It is most often treated with chemotherapy and …

Sirna Knockdown Of Rptor Alters Gene Expression In Ewing Sarcoma Cells, Sergio Cipriano, David Leavitt, Michael Oliva, Liam Valdez

Posters - 2026

Ewing sarcoma is a highly aggressive cancer that primarily affects children and young adults. Although treatment options exist, many patients do not respond effectively, showing the need for improved targeted therapies¹. RPTOR is a key in mTORC1 complex which regulates cell growth, proliferation, and survival². LY2874455 is a selective pan-FGFR inhibitor that targets growth factor signaling pathways involved in tumor progression³, and FGFR signaling interacts with pathways such as mTOR, making it a potential target for combination therapies. We hypothesized that silencing RPTOR in Ewing sarcoma cells would disrupt mTOR signaling and alter expression of genes linked to cell survival …

Availability Of Cancer Screening Across Hiv Treatment Sites In The Iedea Consortium, Rachael Pellegrino, Bryan Shepherd, Sanjay Pujari, Valeria Fink, Gad Murenzi, Miriam Nakalembe, Sally Coburn, Eliane Rohner, Antoine Jaquet, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

Cancer remains a leading cause of morbidity and mortality in people with HIV, and the importance of cancer screening increasesas this population ages. In 2017, 2020, and 2023, cross-sectional surveys were conducted at HIV care sites across 5 continentswithin the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We described cancer screening avail-ability in 2023 and over time for cervical and anal cancer screening using generalized estimating equations with a logit linkfunction to account for site clustering, rurality, and country income. Of the 220 sites in the 2023 survey, 61% (134/220) reportedcervical cancer screening by cytology or human papillomavirus (HPV) …

Concerns Regarding The Efficacy Of Utilizing The Vibrational Response Of Aminocyanine Molecules To Near Infrared Light For Cancer Cell Destruction, Parsa Faghani-Eskandarkolaei, James Welsh, Seyed Ali Reza Mortazavi, Parmis Taghizadeh, Mobina Baramaki, Fatemeh Shams, Mohammed Nasir Abubakari, Seyed Mohammad Javad Mortazavi, Lembit Sihver

Informatics and Engineering Systems Faculty Publications

Recent advancements in cancer treatment have introduced the use of aminocyanine molecules, activated by near-infrared (NIR) light, to induce vibrational responses that can selectively destroy cancer cells. This commentary critically examines a study that reports a 99% efficacy of this method against human melanoma cells in vitro, and significant tumor reduction in murine models. While the findings are promising, our analysis highlights crucial oversights in the study’s implications for clinical applications. Specifically, the persistence of even a small fraction of cancer cells post-treatment poses significant risks for tumor regrowth and acquired resistance. Additionally, the study’s approach neglects the heterogeneity of …

Genome-Wide Crispr Screen Identifies A Cytokine-Enhancer Circuit Driving Hif-2Α Activation In Renal Cancer, Jun Fang, Jeremy M Simon, Tao Wang, Yunpeng Gao, Xianju Bi, Chengheng Liao, Yayoi Adachi, Jin Zhou, Hongyi Liu, Qian Liang, James A Nathan, Ram Mani, James Brugarolas, Qing Zhang

Faculty, Staff and Student Publications

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC). Here, we uncover a cytokine-driven enhancer mechanism that sustains HIF-2α expression through the JAK1-STAT3 signaling pathway. Using a genome-wide CRISPR screen in VHL-deficient ccRCC cells, we identified SOCS3 as a key negative regulator of HIF-2α. Mechanistically, loss of SOCS3 activates JAK1-STAT3 signaling, leading to the recruitment of STAT3 to distal enhancers upstream of EPAS1 that physically loop to its promoter to drive HIF-2α transcription. This cytokine-enhancer circuit was recapitulated in ccRCC patient samples and functionally …

Barriers To Occupational And Physical Therapy Utilization For Children With Cancer, Maria C Swartz, Shiming Zhang, Donna Kelly, Clark R Andersen, Keri Schadler, Eduardo Gonzalez Villarreal, Amy Heaton, Karen Moody

Faculty, Staff and Student Publications

Introduction: Occupational and physical therapy (OT/PT) referrals and utilization barriers for childhood cancer patients have not been adequately examined. The current study investigated factors influencing referrals to and utilization of OT/PT services among children with cancer at an NIH-designated cancer center.

Methods: This retrospective cohort study included pediatric cancer patients (up to 18.99 years) presenting to the center over a 33.5-month period. Variables that could influence referrals to OT/PT were extracted from the electronic medical record (EMR) including OT and PT referrals (inpatient and outpatient), OT and PT consult completion, age at diagnosis, cancer type, sex, race/ethnicity, insurance, cancer treatment, …

Work Challenges And Cancer-Related Cognitive Impairment: Level Of Education Accounts For Unmet Needs Beyond Cognitive Impairment Severity, Darren Haywood, Susan L. Rossell, Ashley Henneghan, Frank D. Baughman, Jennifer Haywood, Evan Dauer, Annika Hegde, Ahmed A. Moustafa, Nicolas H. Hart

Research outputs 2022 to 2026

Purpose: Cancer-related cognitive impairment (CRCI) can impact cancer survivors’ return to work and occupational functioning for many years following the completion of cancer treatment. Understanding the characteristics of CRCI-related occupational difficulties and unmet supportive care needs is critical for the development of effective interventions. Within occupational roles, a higher level of education is typically associated with greater cognitive load and different demands. The objective of this study was to examine whether the level of education accounted for CRCI-related (a) occupational difficulties and (b) occupational unmet supportive care needs, beyond the contributions of perceived cognitive functioning and employment level. Methods: A …

Development And Validation Of A Prognostic Risk Score For Patients With Cancer And Neutropenic Fever Presenting To The Emergency Department, Sandy Nath, Aiham Qdaisat, Andriy Derkach, Afia Babar, Deepti Zalavadia, Patrick Chaftari, Ziyi Li, Monica K Wattana, Joseph Schmeltz, Rocio Perez Johnston, Eduardo Ortiz, Kumar Alagappan, Adam Klotz, Sai-Ching Jim Yeung

Faculty, Staff and Student Publications

Objectives: Neutropenic fever (NF) is a life-threatening oncologic emergency associated with significant morbidity and mortality. Current predictive risk-stratification scores' limitations include outdated criteria, subjectivity, and low usage in the emergency department (ED). We sought to develop and externally validate a pragmatic, objective risk score to predict adverse outcomes in patients presenting to the ED with cancer and NF.

Methods: A retrospective cohort study was performed using data from 2 comprehensive cancer centers. The derivation cohort included adults presenting with NF to Memorial Sloan Kettering Cancer Center. External validation was conducted using data from the MD Anderson Cancer Center. The primary …

Dasatinib Resensitizes Braf/Mek Inhibitor Efficacy In Patient-Derived Xenografts From Patients With Progression On Braf/Mek Inhibitor Treatment, Vito W Rebecca, Min Xiao, Andrew Kossenkov, Tetiana Godok, Gregory Schuyler Brown, Gretchen M Alicea, Hongkai Ji, Marie Portuallo, Jeremy Bravo, Vissy Elad, Yeqing Chen, Eneda Toska, Mitchell E Fane, Kasey L Couts, Jessie Villanueva, Katherine Nathanson, Keerthana M Arun, Govind Warrier, Xiangfan Yin, Jianyi Ding, Qin Liu, Yogesh Goyal, Y N Vashisht Gopal, Michael A Davies, Meenhard Herlyn

Faculty, Staff and Student Publications

Although BRAF/MEK inhibitor (BRAFi/MEKi) therapy initially shows high efficacy in patients with BRAFV600 E/K cutaneous melanoma, resistance develops in over 75% of cases. We tested robustness of the umbrella trial strategy in this population by analyzing relationships between genomic status of a gene and associated downstream consequences at the protein level. The results revealed weak relationships among mutations, copy-number amplification, and protein expression and activation. An in vivo compound repurposing screen using 11 clinically relevant agents from an NCI-portfolio with pan-RTK, non-RTK, and/or PI3K-mTOR specificity identified dasatinib as most capable of restoring sensitivity to BRAFi/MEKi in patient-derived xenograft (PDX) …

Jak/Stat1-Interferon-Isgylation Networks In Breast Cancer Resistance To Inhibitors Of Foxm1 And Cdk4/6, Blake N Plotner, Grace O Pento, Sung Hoon Kim, Alekya Raghavan, Rachel Schiff, John A Katzenellenbogen, Benita S Katzenellenbogen

Faculty, Staff and Students Publications

The oncogenic transcription factor FOXM1 and the cyclin-dependent kinases 4 and 6 all promote cancer progression and aggressiveness that can be suppressed initially by targeted inhibitors, but resistance almost always develops. We show that ER-positive breast cancer cells that acquire resistance to FOXM1 inhibitors (FOXM1i) or CDK4/6 inhibitors (CDK4/6i) exhibit some key similarities including an increased JAK/STAT-interferon-ISGylation signaling network with elevated ISG15 and ISG15 protein conjugates, but with differences in magnitudes and patterns of ISGylated proteins. All the resistant cell lines also express higher levels of enzymes critical for ISGylation which predict poorer survival outcomes in ER-positive breast cancer patients. …

Tumor Targeting With Peptide-Drug Conjugates: Showcasing Key Progress And Hurdles, Keykavous Parang, Thuy Do, Clare Dinh, Dorna Davanidavari, Max Foroughi, Troy Khong, Mahsa Moazen, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs’ small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss …

Prevalence Of Her2-Low Status And Outcomes In Early-Stage Her2-Negative Breast Cancer, Akshara Singareeka Raghavendra, Diane D Liu, Sarah Pasyar, Senthil Damodaran, Yu Shen, Carlos H Barcenas

Faculty, Staff and Student Publications

HER2-low breast cancer (IHC 1+ or 2+ without HER2 gene amplification) is a distinct and understudied subtype. In a cohort of 14,593 early-stage breast cancer patients treated at MD Anderson from 2006 to 2019, 60.4% were HER2-low. Multivariable analysis showed HER2-low status was independently associated with race, histologic subtype, higher nuclear grade and stage, and estrogen receptor (ER) positivity. Among 2464 patients receiving neoadjuvant chemotherapy, HER2-low status was not linked to pathologic complete response (pCR), overall survival (OS), or disease-free survival (DFS) compared to HER2-0 tumors. Factors predicting pCR included nuclear grade III, stage I, invasive ductal carcinoma, lower ER/PR …

Investigating The Oncogenic Role Of Aberrant Ezh2 In Hepatoblastoma, Brian T Hickner, Priyanka Rao, Roma H Patel, Andrew A Badachhape, Somak Roy, Emily Schepers, Nikolai A Timchenko, James I Geller, Sarangarajan Ranganathan, Gregory M Tiao, Bruce Aronow, Takanori Takebe, Sarah E Woodfield, Sanjeev A Vasudevan, Alexander J Bondoc

Faculty, Staff and Students Publications

Hepatoblastoma (HB) is the most common pediatric liver malignancy. However, its cellular origin and molecular drivers remain poorly defined. Using single-nuclear RNA sequencing (snRNA-seq), we identified a proliferative, hepatocyte-derived tumor cell population (cycling HepT) enriched for Enhancer of Zeste Homolog 2 (EZH2) expression, particularly in the aggressive embryonal subtype. Integrative genomic and transcriptomic profiling confirmed EZH2 overexpression. Disruption of the PRC2 complex was evident through mislocalization and reduced expression of SUZ12, a core component. EZH2 overexpression correlated with upregulation of mitotic regulators such as AURKB and Ki67 in human HB gene expression analysis as compared to background liver. Targeted sequencing …