Genetic Phenomena Commons^™

Outcomes Of Treatment With Neoadjuvant Cemiplimab For Patients With Advanced, Resectable Cutaneous Squamous Cell Carcinoma Of The Head And Neck: Secondary Analysis Of A Phase 2 Clinical Trial, Renata Ferrarotto, Priyadharsini Nagarajan, Jacob M Maronge, Jason M Johnson, David I Rosenthal, Jeffrey N Myers, Neil D Gross

Faculty, Staff and Student Publications

This secondary analysis of a phase 2 clinical trial examines long-term survival for resectable cutaneous squamous cell carcinoma of the head and neck according to pathologic response.

A Review Of Pulmonary Neutrophilia And Insights Into The Key Role Of Neutrophils In Particle-Induced Pathogenesis In The Lung From Animal Studies Of Lunar Dusts And Other Poorly Soluble Dust Particles, Chiu-Wing Lam, Vincent Castranova, Kevin Driscoll, David Warheit, Valerie Ryder, Ye Zhang, Patti Zeidler-Erdely, Robert Hunter, Robert Scully, William Wallace, John James, Brian Crucian, Mayra Nelman, Richard Mccluskey, Donald Gardner, Roger Renne, Roger Mcclellan

Faculty, Staff and Student Publications

The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), …

Validation Of A 12-Color Flow Cytometry Assay For Acute Myeloid Leukemia Minimal/Measurable Residual Disease Detection, Sa A Wang, Jeffrey L Jorgensen, Shimin Hu, Fuli Jia, Shaoying Li, Sanam Loghavi, Chi Young Ok, Beenu Thakral, Jie Xu, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

Background: Acute myeloid leukemia (AML) minimal/measurable residual disease (MRD) by multicolor flow cytometry is a complex laboratory developed test (LDT), challenging for implementation. We share our experience in the validation of a 12-color AML MRD flow cytometry assay to meet stringent regulatory requirements.

Methods: We worked under the guidelines of the CLSI HL62 publication, illustrated the details of the validation process that was tailored to uniqueness of AML MRD, and tested its clinical validity in 61 patients. The "trueness" was determined by correlating with concurrent molecular genetic testing and follow-up bone marrow examinations.

Results: Under assay specificity, we shared the …

Inhibition Of Menin, Bcl-2, And Flt3 Combined With A Hypomethylating Agent Cures Npm1/Flt3-Itd/-Tkd Mutant Acute Myeloid Leukemia In A Patient-Derived Xenograft Model, Bing Z Carter, Po Yee Mak, Wenjing Tao, Lauren B Ostermann, Duncan H Mak, Baozhen Ke, Peter Ordentlich, Gerard M Mcgeehan, Michael Andreeff

Faculty, Staff and Student Publications

No abstract provided.

Cobimetinib Plus Vemurafenib In Patients With Solid Tumors With Braf Mutations: Results From The Targeted Agent And Profiling Utilization Registry Study, Funda Meric-Bernstam, Michael Rothe, Pam K Mangat, Elizabeth Garrett-Mayer, Rodolfo Gutierrez, Eugene R Ahn, Timothy L Cannon, Steven Powell, John C Krauss, Christopher M Reynolds, Margaret Von Mehren, Deepti Behl, Carmen J Calfa, Herbert L Duvivier, Henry G Kaplan, Michael B Livingston, Manish R Sharma, Walter J Urba, Gina N Grantham, Dominique C Hinshaw, Abigail Gregory, Susan Halabi, Richard L Schilsky

Faculty, Staff and Student Publications

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported.

Methods: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of …

Important Considerations For Real-World Analysis Of Neurotrophic Tyrosine Receptor Kinase Fusion Cancer And Tropomyosin Receptor Kinase Inhibitors, Marcia S Brose, David S Hong, Alexander Drilon

Faculty, Staff and Student Publications

No abstract provided.

Adagrasib In Advanced Solid Tumors Harboring A Krasg12c Mutation, Tanios S Bekaii-Saab, Rona Yaeger, Alexander I Spira, Meredith S Pelster, Joshua K Sabari, Navid Hafez, Minal Barve, Karen Velastegui, Xiaohong Yan, Aditya Shetty, Hirak Der-Torossian, Shubham Pant

Faculty, Staff and Student Publications

Purpose: Adagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.

Methods: In this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response …

Zranb1 Is An Nbs1 Deubiquitinase And A Potential Target To Overcome Radioresistance And Parp Inhibitor Resistance In Triple-Negative Breast Cancer, Ying Mei, Qinglei Hang, Hongqi Teng, Fan Yao, Mei-Kuang Chen, Mien-Chie Hung, Yutong Sun, Li Ma

Faculty, Staff and Student Publications

No abstract provided.

Diversity, Equity, And Inclusion In The Melanoma Research Community, Marie E Portuallo, David Y Lu, Gretchen M Alicea, Joel Bolling, Rebecca Lee, Jennifer Mcquade, Allison Betof Warner, Michael Davies, Ashani Weeraratna, Jessie Villanueva, Vito W Rebecca

Faculty, Staff and Student Publications

The inaugural Diversity and Inclusion in Science Session was held during the 2021 Society for Melanoma Research (SMR) congress. The goal of the session was to discuss diversity, equity, and inclusion in the melanoma research community and strategies to promote the advancement of underrepresented melanoma researchers. An international survey was conducted to assess the diversity, equity, and inclusion (DEI) climate among researchers and clinicians within the Society for Melanoma Research (SMR). The findings suggest there are feelings and experiences of inequity, bias, and harassment within the melanoma community that correlate with one's gender, ethnic/racial group, and/or geographic location. Notably, significant …

Safety, Efficacy, And Pk/Pd Of Vorasidenib In Previously Treated Patients With Midh1/2 Hematologic Malignancies: A Phase 1 Study, Courtney D Dinardo, Stéphane De Botton, Daniel A Pollyea, Richard M Stone, Jessica K Altman, Amir T Fathi, Tharin Limsakun, Min Liang, Sung Choe, Mohammad Hossain, Adriana E Tron, Qian Meng, Stephanie M Kapsalis, Shuchi S Pandya, Eytan M Stein

Faculty, Staff and Student Publications

No abstract provided.

Safety, Tolerability, And Clinical Activity Of Selinexor In Combination With Pembrolizumab In Treatment Of Metastatic Non-Small Cell Lung Cancer, Mehmet Altan, Janet Tu, Denái R Milton, Bulent Yilmaz, Yanyan Tian, Frank V Fossella, Frank E Mott, George R Blumenschein, Bettzy Stephen, Daniel D Karp, Funda Meric-Bernstam, John V Heymach, Aung Naing

Faculty, Staff and Student Publications

Background: In lung cancer, overexpression of nuclear export proteins can result in inactivation of critical tumor suppressor proteins and cell-cycle regulators. Selective suppression of nuclear export proteins has immunomodulatory activities. Here, clinical safety and early efficacy data are presented on the combination of pembrolizumab and an oral selective nuclear export inhibitor, selinexor, for the treatment of metastatic non-small cell lung cancer (mNSCLC).

Methods: The primary objective of this prospective investigator-initiated study was to determine the safety and tolerability of selinexor in combination with pembrolizumab in patients with mNSCLC. Secondary objectives included determination of objective tumor response rate, disease control rate, …

Vascularized Hepatocellular Carcinoma On A Chip To Control Chemoresistance Through Cirrhosis, Inflammation And Metabolic Activity, Alican Özkan, Danielle L Stolley, Erik N K Cressman, Matthew Mcmillin, Thomas E Yankeelov, Marissa Nichole Rylander

Faculty, Staff and Student Publications

Understanding the effects of inflammation and cirrhosis on the regulation of drug metabolism during the progression of hepatocellular carcinoma (HCC) is critical for developing patient-specific treatment strategies. In this work, we created novel three-dimensional vascularized HCC-on-a-chips (HCCoC), composed of HCC, endothelial, stellate, and Kupffer cells tuned to mimic normal or cirrhotic liver stiffness. HCC inflammation was controlled by tuning Kupffer macrophage numbers, and the impact of cytochrome P450-3A4 (CYP3A4) was investigated by culturing HepG2 HCC cells transfected with CYP3A4 to upregulate expression from baseline. This model allowed for the simulation of chemotherapeutic delivery methods such as intravenous injection and transcatheter …

Evolving Trends And Outcomes In Older Patients With Acute Myeloid Leukemia Including Allogeneic Stem Cell Transplantation, Alexandre Bazinet, Hagop Kantarjian, Naszrin Arani, Uday Popat, Alex Bataller, Koji Sasaki, Courtney D Dinardo, Naval Daver, Musa Yilmaz, Hussein A Abbas, Nicholas J Short, Ghayas Issa, Elias Jabbour, Sherry A Pierce, Julianne Chen, Ricky Garcia, Marina Konopleva, Guillermo Garcia-Manero, Amin Alousi, Elizabeth J Shpall, Richard E Champlin, Gautam Borthakur, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Outcomes in older patients with acute myeloid leukemia (AML) have historically been poor. Given advances in low-intensity therapy (LIT) and stem cell transplantation (SCT), we performed a retrospective single-center study to evaluate the contemporary outcomes of this population. We reviewed all patients ≥60 years with newly diagnosed AML between 2012 and 2021 and analyzed treatment and SCT-related trends and outcomes. We identified 1073 patients with a median age of 71 years. Adverse clinical and cytomolecular findings were frequent within this cohort. In total, 16% of patients were treated with intensive chemotherapy, 51% with LIT alone, and 32% with LIT plus …

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

Identification Of New Aptamer Bc-3 Targeting Rps7 From Rapid Screening For Bladder Carcinoma, Yunyi Liu, Juan Li, Hailong Ou, Dan Qi, Bei Hu, Yuxi Xu, Jian Hu, Yi Xiong, Luling Xia, Jason H Huang, Xiaoxiao Hu, Erxi Wu

Faculty, Staff and Student Publications

Aptamers, short single DNA or RNA oligonucleotides, have shown immense application potential as molecular probes for the early diagnosis and therapy of cancer. However, conventional cell-SELEX technologies for aptamer discovery are time-consuming and laborious. Here we discovered a new aptamer BC-3 by using an improved rapid X-Aptamer selection process for human bladder carcinoma, for which there is no specific molecular probe yet. We show that BC-3 exhibited excellent affinity in bladder cancer cells but not normal cells. We demonstrate that BC-3 displayed high selectivity for tumor cells over their normal counterparts in vitro, in mice, and in patient tumor …

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …

Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylatio, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler

Faculty, Staff and Student Publications

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a …

Autotaxin Suppresses Cytotoxic T Cells Via Lpar5 To Promote Anti-Pd-1 Resistance In Non-Small Cell Lung Cancer, Jessica M Konen, B Leticia Rodriguez, Haoyi Wu, Jared J Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I Wistuba, Jianjun Zhang, Don L Gibbons

Faculty, Staff and Student Publications

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and …

A Single Dominant Locus Restricts Retrovirus Replication In Ybr/Ei Mice, Helen A Beilinson, Amanda Sevilleja, Jessica Spring, Fernando Benavides, Vera Beilinson, Nickolas Neokosmidis, Tatyana Golovkina

Faculty, Staff and Student Publications

Differential responses to viral infections are influenced by the genetic makeup of the host. Studies of resistance to retroviruses in human populations are complicated due to the inability to conduct proof-of-principle studies. Inbred mouse lines, which have a range of susceptible phenotypes to retroviruses, are an ideal tool to identify and characterize mechanisms of resistance and define their genetic underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, a mucosally transmitted murine retrovirus, but eliminate the virus from their pedigrees. Virus elimination correlates with a lack of virus-specific neonatal oral tolerance, which is a major mechanism for blocking the …

Archival Single-Cell Genomics Reveals Persistent Subclones During Dcis Progression, Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M Tran, Aatish Thennavan, Min Hu, Anna K Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M King, Vandna Shah, Petra Kristel, Carolien L Van Der Borden, Jeffrey R Marks, Yuehui Zhao, Amado J Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L Gibbons, Ellinor Sawyer, Alastair M Thompson, Andrew Futreal, E Shelley Hwang, Jelle Wesseling, Esther H Lips, Nicholas E Navin

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary …

Pan-Cancer Analysis Of Post-Translational Modifications Reveals Shared Patterns Of Protein Regulation, Yifat Geffen, Shankara Anand, Yo Akiyama, Tomer M Yaron, Yizhe Song, Jared L Johnson, Akshay Govindan, Özgün Babur, Yize Li, Emily Huntsman, Liang-Bo Wang, Chet Birger, David I Heiman, Qing Zhang, Mendy Miller, Yosef E Maruvka, Nicholas J Haradhvala, Anna Calinawan, Saveliy Belkin, Alexander Kerelsky, Karl R Clauser, Karsten Krug, Shankha Satpathy, Samuel H Payne, D R Mani, Michael A Gillette, Saravana M Dhanasekaran, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Ana I Robles, Steven A Carr, Alexander J Lazar, François Aguet, Lewis C Cantley, Li Ding, Gad Getz, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with …

Pan-Cancer Proteogenomics Connects Oncogenic Drivers To Functional States, Yize Li, Eduard Porta-Pardo, Collin Tokheim, Matthew H Bailey, Tomer M Yaron, Vasileios Stathias, Yifat Geffen, Kathleen J Imbach, Song Cao, Shankara Anand, Yo Akiyama, Wenke Liu, Matthew A Wyczalkowski, Yizhe Song, Erik P Storrs, Michael C Wendl, Wubing Zhang, Mustafa Sibai, Victoria Ruiz-Serra, Wen-Wei Liang, Nadezhda V Terekhanova, Fernanda Martins Rodrigues, Karl R Clauser, David I Heiman, Qing Zhang, Francois Aguet, Anna P Calinawan, Saravana M Dhanasekaran, Chet Birger, Shankha Satpathy, Daniel Cui Zhou, Liang-Bo Wang, Jessika Baral, Jared L Johnson, Emily M Huntsman, Pietro Pugliese, Antonio Colaprico, Antonio Iavarone, Milan G Chheda, Christopher J Ricketts, David Fenyö, Samuel H Payne, Henry Rodriguez, Ana I Robles, Michael A Gillette, Chandan Kumar-Sinha, Alexander J Lazar, Lewis C Cantley, Gad Getz, Li Ding

Faculty, Staff and Student Publications

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of …

Wearable Biosensor With Molecularly Imprinted Conductive Polymer Structure To Detect Lentivirus In Aerosol, Jaskirat Singh Batra, Ting-Yen Chi, Mo-Fan Huang, Dandan Zhu, Zheyuan Chen, Dung-Fang Lee, Jun Kameoka

Faculty, Staff and Student Publications

The coronavirus disease (COVID-19) pandemic has increased pressure to develop low-cost, compact, user-friendly, and ubiquitous virus sensors for monitoring infection outbreaks in communities and preventing economic damage resulting from city lockdowns. As proof of concept, we developed a wearable paper-based virus sensor based on a molecular imprinting technique, using a conductive polyaniline (PANI) polymer to detect the lentivirus as a test sample. This sensor detected the lentivirus with a 4181 TU/mL detection limit in liquid and 0.33% to 2.90% detection efficiency in aerosols at distances ranging from 30 cm to 60 cm. For fabrication, a mixture of a PANI monomer …

Mapping The Evolution Of T Cell States During Response And Resistance To Adoptive Cellular Therapy, Pavan Bachireddy, Elham Azizi, Cassandra Burdziak, Vinhkhang N Nguyen, Christina S Ennis, Katie Maurer, Cameron Y Park, Zi-Ning Choo, Shuqiang Li, Satyen H Gohil, Neil G Ruthen, Zhongqi Ge, Derin B Keskin, Nicoletta Cieri, Kenneth J Livak, Haesook T Kim, Donna S Neuberg, Robert J Soiffer, Jerome Ritz, Edwin P Alyea, Dana Pe'er, Catherine J Wu

Faculty, Staff and Student Publications

No abstract provided.

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

Bicuspid Aortic Valve And Thoracic Aortic Disease: Further Evidence Of Clinically Silent But Deadly Risk To Family Members Of Affected Individuals, Siddharth K Prakash, Hector I Michelena, Dianna M Milewicz

Faculty, Staff and Student Publications

No abstract provided.

Triple-Negative Breast Tumors Are Dependent On Mutant P53 For Growth And Survival, Denada Dibra, Sydney M Moyer, Adel K El-Naggar, Yuan Qi, Xiaoping Su, Guillermina Lozano

Faculty, Staff and Student Publications

The TP53 tumor suppressor gene is mutated early in the majority of patients with triple-negative breast cancer (TNBC). The most frequent TP53 alterations are missense mutations that contribute to tumor aggressiveness. We developed an autochthonous somatic K14-Cre driven TNBC mouse model with p53R172H and p53R245W mutations in which mutant p53 can be toggled on and off genetically while leaving the tumor microenvironment intact and wild-type for p53. These mice develop TNBCs with a median latency of 1 y. Deletion of mutant p53R172H or p53R245W in vivo in these tumors blunts their tumor growth and significantly extends survival of mice. Downstream …

Pirtobrutinib In Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma, Michael L Wang, Wojciech Jurczak, Pier Luigi Zinzani, Toby A Eyre, Chan Y Cheah, Chaitra S Ujjani, Youngil Koh, Koji Izutsu, James N Gerson, Ian Flinn, Benoit Tessoulin, Alvaro J Alencar, Shuo Ma, David Lewis, Ewa Lech-Maranda, Joanna Rhodes, Krish Patel, Kami Maddocks, Nicole Lamanna, Yucai Wang, Constantine S Tam, Talha Munir, Hirokazu Nagai, Francisco Hernandez-Ilizaliturri, Anita Kumar, Timothy S Fenske, John F Seymour, Andrew D Zelenetz, Binoj Nair, Donald E Tsai, Minna Balbas, Richard A Walgren, Paolo Abada, Chunxiao Wang, Junjie Zhao, Anthony R Mato, Nirav N Shah

Faculty, Staff and Student Publications

Purpose: Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis.

Methods: Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety. …