Medicine and Health Sciences Commons^™

Toxicological Effects And Treatment Of Accidental Ingestion Of Simparica Trio® In Felis Catus: An Investigative Review, Aussia Stander

Honors Theses

Simparica TRIO^®, a canine endectocide manufactured by Zoetis, contains sarolaner, moxidectin, and pyrantel pamoate salt in an orally administered chewable tablet. These compounds are all toxic to both cats and dogs in sufficient amounts. As Simparica TRIO^® rises in popularity among pet owners, Felis catus (felines, cats) in multi-pet households (households with both cats and dogs) are at increased risk of overdosage and toxicosis from accidental ingestion of Simparica TRIO^® due to their smaller weight.

Simparica TRIO^® is not for feline use and little literature exists on the symptoms of and treatment for accidental ingestion …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

Stop Horsing Around: A Case Of Cenbuterol Toxicity, Justin Sanchez, Mark Cheneler, Alexandra Villacres

North Texas Research Forum 2024

Introduction: Clenbuterol is a medication that is relatively unknown outside of the equestrian and bodybuilding worlds. It acts as a sympathomimetic compound with beta-2 agonism and can cause tachycardia and bronchodilation. It is utilized for this bronchodilation as a means of improving equestrian performance. Its sympathomimetic effects were utilized in the bodybuilding community as a weight loss medication by increasing catabolic metabolism. Here we present a case of intentional clenbuterol toxicity for weight loss. Case presentation: A 34-year-old woman with past medical history of migraines presented to the emergency department for evaluation of palpitations and an EKG showed sinus …

Subchronic Toxicity Study Of Sterculia Rubiginosa Zoll. Ex Miq. Leaves Extract, Rini Prastiwi, Ester Hidayati, Riska Anggraini, Cut Mauliza, Ita Anggraini, Ema Dewanti

Pharmaceutical Sciences and Research

Ki hampelas (Sterculia rubiginosa Zoll. Ex Miq.) is traditionally used as an antiasthma. It also reported has antioxidant and nephroprotective activity. This study was conducted to evaluate the subchronic toxicity of the leaf extract of ki hampelas. The extract was orally administered to male and female Sprague-Dawley rats at doses of 50, 200, and 400 mg/kg bodyweight (BW) per day for 28 days. The rats were divided into four groups, consist of consist of normal group (Na CMC 0.5%), dose 1 (50 mg/kg BW), dose 2 (200 mg/kg BW), and dose 3 (400 mg/ kg BW) of extract. The …

Insulin In Combination With N-Acetylcysteine Protects Hypoxia-Induced Toxicity In 661w Cells, Lili M. Guerra, Laura Valdez, Benxu Cheng, Andrew Tsin

Research Colloquium

Background: Proliferative diabetic retinopathy (PDR) is the leading cause of blindness among working-age adults. Photoreceptors are the most numerous and metabolically demanding cells in the retina thus oxygen is essential for retinal function. It has been reported that photoreceptors found in rat retina are specifically vulnerable to hypoxia. Hypoxia-induced metabolic stress leads to photoreceptor atrophy and retinopathy. Furthermore, photoreceptor cell death is known to occur mainly through apoptosis. However, the protection of hypoxia-induced-cytotoxicity in cone photoreceptor cells has not been investigated extensively. The aim of this study was to determine whether co-treatment of insulin and the N-Acetyl-L-Cysteine (NAC) (a free …

Dpyd Pathogenic Variants Associated With Fluoropyrimidines Toxicity, Diana Cristina Pérez-Ibave, Noé Israel Oliva-García, Irasema Ramos-Martínez, Francisco Javier Villarreal Alvarado, Valeria Jimena Gómez Ordaz, Jonatán Isaí Cortes Alfaro, Carlos Horacio Burciaga-Flores, Juan Francisco González-Guerrero, Oscar Vidal-Gutiérrez, Maria De Lourdes Garza-Rodriguez

Research Symposium

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown.

Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer's recommendations. We …

Gold Nanoparticle-Based Strategies Against Sars-Cov-2: A Review, Yousef Rasmi, Kevser K. Kırboğa, Johra Khan, Ena Gupta, Fadia Mostafa, Murali M. Yallapu, Fernanda Pilaquinga

School of Medicine Publications and Presentations

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 has been an immense threat to global public health and has also had a negative socioeconomic impact worldwide. However, although the pandemic is now under control, it has demonstrated that society is unprepared to use analysis methods that are applicable to various types of viruses nor apply new therapies to prevent infections, considering the extensive time needed for vaccine development. The use of nanomaterial-based diagnostics and therapeutics can provide essential strategies for both virus detection and treatment. Gold nanoparticles (AuNPs) are the nanomaterials most commonly used to enhance virus …

The Biocompatibility Of A Ginger-Containing Herbal Toothpaste On Developing Zebrafish Embryos, Simge Meseli, Unsal Veli Ustundag, Perihan Seda Ates, Ismail Unal, Ebru Isik Alturfan, Dilek Tağtekin, Funda Yanikoglu

Journal of Dentistry Indonesia

The biocompatibility of toothpaste in an oral cavity should be approved by clinical trials. Nowadays, herbal toothpaste is increasing in popularity due to its natural ingredients. Being genetically similar to humans, zebrafish are used in potential toxicity testing. The zebrafish embryotoxicity test is a fast and straightforward method to study chemical toxicity during embryogenesis.

Objective: This study aimed to evaluate if there was any biocompatibility of the toothpaste on zebrafish embryos.

Methods: Adult AB strain zebrafish were used according to Institutional Animal Care and Use Committee protocols. Normally dividing, spherical embryos were exposed to herbal toothpaste with ginger (Gumgumix, Turkey) …

The Role Of Pharmacogenetics On Breast Cancer Treatment Efficacy And Toxicity, Noor Alani

Doctor of Medical Science (DMSc)

Purpose: This research article aims to shed light on the pivotal role of pharmacogenetics in breast cancer treatment by examining genetic variations that influence the efficacy and toxicity of commonly used drugs. Furthermore, this study highlights the significance of personalized treatment approaches in optimizing patient outcomes.

Method: A comprehensive literature search was conducted using databases such as PubMed. Search terms included "pharmacogenetics," "breast cancer treatment," "genetic markers," and "adverse effects." This review critically analyzes relevant studies that focus on the impact of genetic variations on the response to drugs used in breast cancer treatment.

Results: The review …

Adverse Effects And Pharmacokinetic Characteristics Of High-Dose Glucocorticoid Treatment In Children With Rheumatic Diseases, Renee X. Pang

Electronic Thesis and Dissertation Repository

This integrated-article thesis explores the impact of long-term glucocorticoid (GC) therapy on children with RD. Long-term GC treatment is potentially associated with severe adverse drug reactions (ADRs). Our scoping review summarizes the current evidence health-related quality of life (HRQOL) impacts of this treatment on children with RD. We describe the frequency of ADRs related to long-term GC treatment in a convenience sample of pediatric RD patients on long-term prednisone therapy and evaluate clinical characteristics that may be associated with risk for of GC-related ADRs. Lastly, we present a pilot study to evaluate the feasibility of monitoring GC PK in children …

Metformin-Associated Lactic Acidosis: A Case Report, Joshua Santoli, Jamie Lee Aldakkour, Hossein Tohidi, Yizhi Lin

HCA Healthcare Journal of Medicine

Introduction

Metformin is considered a first-line therapy for patients with diabetes secondary to its cost efficiency, minimal side effects, and marked improvement in one’s hemoglobin A1c; however, metformin is avoided in patients with renal insufficiency out of concern for drug accumulation and lactic acidosis. In fact, there is a black box warning for metformin, identifying lactic acidosis as the inciting trigger for fatal arrhythmias and death.

Case Presentation

A 62-year-old male presented with multiple episodes of nausea, vomiting, abdominal pain, and decreased urine output for 3 days after working on a roof, all day in the summer heat. He did …

Detectable Ctdna At The Time Of Treatment Cessation Of Ipilimumab And Nivolumab For Toxicity Predicts Disease Progression In Advanced Melanoma Patients, Lydia Warburton, Anna Reid, Benhur Amanuel, Leslie Calapre, Michael Millward, Elin Gray

Research outputs 2022 to 2026

Background: Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context. Methods: This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Sciences & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Impaired Cytokines Gene Expression By Diazinon And Its Relation With Blood Chemistry And Oxidative Stress Biomarkers In Nile Tilapia (Oreochromis Niloticus), Mahmoud El Sebaei, Mohammad Shathele, Sabry Mohamed El-Bahr

The Thai Journal of Veterinary Medicine

Diazinon (DZN) is a promising broad-spectrum organophosphorus insecticide. There is no evidence to support the hypothesis that DZN alters cytokine gene expression and that these modifications have an immediate impact on the histopathology, blood chemistry and oxidative stress in Nile tilapia (Oreochromis niloticus). Therefore, 225 fish were divided into one control group and four treatment groups (45 fish/group; 3 replicates/group; 15 fish/ replicate). Fish in the control group were supplied with water free of DZN. Fish in the treatment groups (T1-T4) were intoxicated with DZN at 0.28 mg/L for 1, 2, 3 and 4 weeks, respectively. Activities of AST and …

Health Effects Of Neonicotinoids On An Agricultural Community, Jocelyn Rodriguez-Paar

Capstone Experience

Mead, Nebraska, a small United States agricultural community consisting of approximately 600 people, was accidentally exposed to high amounts of neonicotinoids when AltEn, an ethanol plant that used neonicotinoid coated corn and soybean seeds for biofuel, was discovered not disposing of the toxic byproduct safely. Coincidentally, there was also a leak in their wastewater system that also contaminated the nearby areas. Although neonicotinoids are not considered highly dangerous with low dose exposures, large dose exposures can cause symptoms similarly to nicotine poisonings, such as difficulty breathing, vomiting, nausea, hypertension, tachycardia, and lethargy (Imamura, T. et al., 2010). Neonicotinoid poisoning can …

Berberis Aristata And Its Secondary Metabolites: Insights Into Nutraceutical And Therapeutical Applications, Firdaus Jahan, Sahir Sultan Alvi, Mohammad Hayatul Islam

School of Medicine Publications and Presentations

Considering the rising global health challenges and public expectations in terms of safety and cost effectiveness, it is necessary to promote effective, safer and cheaper alternative treatment options, particularly to benefit low- and middle-income countries (LMICs). Therapeutic regimens implying natural sources i.e., plants and their secondary metabolites have been trusted by a large proportion of sufferers and extensively searched for their pharmacological actions. Berberis aristata, commonly known as Zarishk, Daruharidra and Indian barberry, is being used in traditional medicine systems across the globe, particularly Asian countries i.e., India and China, and has also gained much attention …

Structural Elucidation And Toxicity Evaluation Of Bioactive Compounds From The Leaves And Stem Woods Of Synadenium Glaucescens Pax., David Credo, Faith Philemon Mabiki, Francis Machumi, Claus Cornett

Pharmaceutical Sciences and Research

The leaves and stem woods of Synadenium glaucescens Pax. are traditionally used for treatment of various human diseases in Tanzania. However, there is limited information on the structural elucidation and toxicity properties of bioactive compounds responsible for their pharmacological properties. Thus, this study was aimed to elucidate and evaluate toxicity properties of bioactive compounds from these parts. Separation of bioactive compounds was achieved by using column chromatographic method, whereas their structures were determined by GC-MS and NMR data and by comparing with literature spectroscopic data. Toxicity properties of isolated compounds was done by brine shrimp lethality test (BSLT) method. In …

Ethanol Leaf Extract Of Hoslundia Opposita In In Vivo Antioxidant And Hepatoprotective Activity Using An Animal Model, Fred Coolborn Akharaiyi, Odoligie Imarhiagbe, Lucky Efe Isunu, Adebayo Thomas Ajibola

BioMedicine

Introduction and aim: The liver is a useful organ that is responsible for the detoxification of harmful substances from the body. Its vital role is of importance hence it should be protected from damages in order to function normally. The management of liver diseases with orthodox medicine has been found to have side effects thus its effective management with folklore has been found better.

Materials and Methods: The leaves of H. oppisota harvested from a forest was processed and extracted with ethanol. The extract concentrations of 100 to 400 mg/ml was used to evaluate acute toxicity, biochemical analysis, …

Recent Progress In Immunotherapy For Skin Cancer, Fadhli Aulia Mughni, Rinadewi Astriningrum, Aida Sd Hoemardani, Kusmarinah Bramono, Adhimukti T. Sampurna, Agassi Suseno Sutarjo

Journal of General - Procedural Dermatology & Venereology Indonesia

Skin cancer is a global health concern due to its growing incidence and high mortality rate. The most common therapeutic modalities in skin cancer include surgery, radiotherapy, and chemotherapy. However, those therapies do not specifically target cancer cells and may damage healthy tissues. Cancer induces immune response by releasing soluble antigens and danger signals caused by tumor cellular stress or death, while the immune system continuously monitor and control malignant proliferation through cancer immunoediting. Therefore, targeting this mechanism is a promising approach to manage cancer, especially those unresponsive to conventional therapies. Immunotherapy is a specific therapy that manipulates the immune …

Digoxin Toxicity And Acute Renal Failure In A 75 Year-Old Female, Daniel Zaayenga, Andrew Caravello, Nicholas Tomasello

Rowan-Virtua Research Day

Digoxin toxicity can present with varying manifestations. While pathognomonic symptoms such as xanthopsia (object appearing yellow) are a board favorite it is not a required finding and is in fact not seen with most patients. Rather digoxin toxicity presents with more non-specific symptoms such as GI distress (anorexia, N/V) neurological distress (lethargy, fatigue, delirium, confusion, disorientation, weakness. EKG findings are varied and include premature ventricular contractions, bradycardia, atrial tachyarrhythmias with AV block, ventricular bigeminy, junctional rhythms, various degrees of AV nodal blockade, ventricular tachycardia, and ventricular fibrillation. Although rarely seen, digoxin is one of the only causes of bidirectional ventricular …

Airborne And Dermal Collection Methods Of Gunshot Residue For Toxicity Studies, Samuel Cole Smith, Oscar Beau Black, Courtney Roper

Faculty and Student Publications

Gunshot residue (GSR) has potential negative health effects on humans as a result of inhalation and dermal exposure to the chemical and physical characteristics of GSR such as Pb, Sb, Ba, nitrocellulose, nitroglycerine, and particulate size fraction. Filter (size selective) and double-sided tape (non-size selective) samples collected airborne GSR during single and triple firing of a 0.22 caliber revolver. Dermal exposures were considered using hand swabs and de-leading wipes, designed to remove the heavy metals. The samples underwent analysis to investigate physical (morphology, size distribution, zeta potential), chemical (black carbon and element concentrations), and potential to induce oxidative stress (oxidative …

Dose-Intensified Stereotactic Ablative Radiation For Localized Prostate Cancer, Lily Chen, Bhavani S. Gannavarapu, University Of Texas Southwestern Medical Center At Dallas, Michael R. Folkert, Michael Dohopolski, Ang Gao, Chul Ahn, Jeffrey Cadeddu, Aditya Bagrodia

School of Medicine Publications and Presentations

Purpose: Stereotactic ablative radiation (SAbR) has been increasingly used in prostate cancer (PCa) given its convenience and cost efficacy. Optimal doses remain poorly defined with limited prospective comparative trials and long-term safety/efficacy data at higher dose levels. We analyzed toxicity and outcomes for SAbR in men with localized PCa at escalated 45 Gy in 5 fractions.

Methods and Materials: This study retrospectively analyzed men from 2015 to 2019 with PCa who received linear-accelerator-based SAbR to 45 Gy in 5 fractions, along with perirectal hydrogel spacer, fiducial placement, and MRI-based planning. Disease control outcomes were calculated from end of treatment. Minimally …

Realistic And Critical Review Of The State Of Systemic Anti-Microbial Peptides, Guangshun Wang, Abraham F. Mechesso

Journal Articles: Pathology and Microbiology

Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility …

Development Of Zafirlukast Derivatives Active Against Porphyromonas Gingivalis, Kaitlind C. Howard

Theses and Dissertations--Pharmacy

Periodontal diseases are inflammatory diseases that can lead to damage of the soft tissue and bone supporting the teeth. Gingivitis is the reversible early stage of gum disease, which consist of gums that bleed when brushing or flossing teeth. When left untreated, the preventable but irreversible late stage of periodontal disease, periodontitis, can lead teeth to loosen or even fall out. Oral bacterial species, such as the Gram-negative anaerobic pathogen Porphyromonas gingivalis trigger these inflammatory diseases through oral dysbiosis. P. gingivalis is a keystone pathogen, meaning that the damage caused by P. gingivalis is not proportional to its abundance. Treatment …

Practices Of Vitamin D Supplementation Leading To Vitamin D Toxicity: Experience From A Low-Middle Income Country, Siraj Muneer, Imran Siddiqui, Hafsa Majid, Nawazish Zehra, Lena Jafri, Aysha Habib

Department of Pathology and Laboratory Medicine

Introduction: The trend of prescribing VD preparations for nonspecific body aches and self-medication has increased significantly. The importance of vitamin D toxicity (VDT) has been underestimated and under recognized. This study was done to determine the frequency toxicity (>150 ng/ml) in subjects for 25-hydroxyvitamin D (25OHD) and evaluate the vitamin D (VD) supplements used by these subjects.
Methodology: This descriptive cross-sectional study was conducted at the Section of Chemical Pathology, Aga Khan University Hospital Karachi from April 2020 to March 2021. Subjects with 25OHD toxicity were contacted and information related to history of calcium and VD supplementation were collected. …

Occurrence, Toxicity And Adsorptive Removal Of The Chloramphenicol Antibiotic In Water: A Review, Luan Minh Nguyen, Ngoan Thi Thao Nguyen, Thuy Thi Thanh Nguyen, Thuong Thi Nguyen, Duyen Thi Cam Nguyen, Thuan Van Tran

Journal Articles

Chloramphenicol is a broad-spectrum bacterial antibiotic used against conjunctivitis, meningitis, plague, cholera, and typhoid fever. As a consequence, chloramphenicol ends up polluting the aquatic environment, wastewater treatment plants, and hospital wastewaters, thus disrupting ecosystems and inducing microbial resistance. Here, we review the occurrence, toxicity, and removal of chloramphenicol with emphasis on adsorption techniques. We present the adsorption performance of adsorbents such as biochar, activated carbon, porous carbon, metal-organic framework, composites, zeolites, minerals, molecularly imprinted polymers, and multi-walled carbon nanotubes. The effect of dose, pH, temperature, initial concentration, and contact time is discussed. Adsorption is controlled by π-π interactions, donor-acceptor interactions, …

Dual Contribution Of The Gut Microbiome To Immunotherapy Efficacy And Toxicity: Supportive Care Implications And Recommendations, Hannah R. Wardill, Raymond J. Chan, Alexandre Chan, Dorothy Keefe, Samuel P. Costello, Nicolas H. Hart

Research outputs 2022 to 2026

The efficacy of immune checkpoint inhibitors (immunotherapy) is increasingly recognized to be linked to the composition the gut microbiome. Given the high rates of resistance, interventions targeting the gut microbiome are now being investigated for its ability to improve the efficacy of immunotherapy. In light of recently published data demonstrating a strong correlation between the efficacy and toxicity of immunotherapy, there is a risk that efforts to enhance immunotherapy efficacy may be undermined by increases in immune-related adverse events (IrAEs) This is particularly important for microbial interventions aimed at increasing immunotherapy efficacy, with many microbes implicated in tumour response also …

Direct Nose To The Brain Nanomedicine Delivery Presents A Formidable Challenge, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular …

Characterization Of Lithium Toxicity At A Large Academic Medical Institution, Melissa R. Vesey, Marian Matalka, Sarah Goldsborough, Mark F. Lutz, John Zaccardelli

Conference Presentation Abstracts

No abstract provided.

Short-Term Treatment With Multi-Drug Regimens Combining Braf/Mek-Targeted Therapy And Immunotherapy Results In Durable Responses In Braf-Mutated Melanoma, Michael G. White, Robert Szczepaniak Sloane, Russell G. Witt, Alexandre Reuben, Pierre Olivier Gaudreau, Miles C. Andrews, Ningping Feng, Sarah Johnson, Caleb Class, Christopher Bristow, Khalida Wani, Courtney Hudgens, Luigi Nezi, Teresa Manzo, Mariana Pettaccia De Macedo, Jianhua Hu, Richard Davis, Hong Jiang, Peter Prieto, Elizabeth Burton, Patrick Hwu, Hussein Tawbi, Jeffrey Gershenwald, Alexander J. Lazar, Michael T. Tetzlaff, Willem Overwijk, Scott E. Woodman, Zachary A. Cooper, Joseph R. Marszalek, Michael A. Davies, Timothy P. Heffernan, Jennifer A. Wargo

Scholarship and Professional Work – COPHS

Targeted and immunotherapy regimens have revolutionized the treatment of advanced melanoma patients. Despite this, only a subset of patients respond durably. Recently, combination strategies of BRAF/MEK inhibitors with immune checkpoint inhibitor monotherapy (α-CTLA-4 or α-PD-1) have increased the rate of durable responses. Based on evidence from our group and others, these therapies appear synergistic, but at the cost of significant toxicity. We know from other treatment paradigms (e.g. hematologic malignancies) that combination strategies with multi-drug regimens (>4 drugs) are associated with more durable disease control. To better understand the mechanism of these improved outcomes, and to identify and prioritize …