Oncology Commons^™

Molecular Landscape And Actionable Alterations In A Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis For Therapy Choice (Nci-Match)., Keith T Flaherty, Robert J Gray, Alice P Chen, Shuli Li, Lisa M Mcshane, David Patton, Stanley R Hamilton, P Mickey Williams, A John Iafrate, Jeffrey Sklar, Edith P Mitchell, Lyndsay N Harris, Naoko Takebe, David J Sims, Brent Coffey, Tony Fu, Mark Routbort, James A Zwiebel, Larry V Rubinstein, Richard F Little, Carlos L Arteaga, Robert Comis, Jeffrey S Abrams, Peter J O'Dwyer, Barbara A Conley

Department of Medical Oncology Faculty Papers

PURPOSE: Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel, single-arm, phase II subprotocols.

PATIENTS AND METHODS: Tumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites were analyzed centrally with …

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling., Rakshamani Tripathi, Zulong Liu, Aditi Jain,, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Department of Medical Oncology Faculty Papers

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2^{nd …}

Photodynamic Therapy In Ocular Oncology., Mehdi Mazloumi, Lauren A Dalvin, Seyed-Hossein Abtahi, Negin Yavari, Antonio Yaghy, Arman Mashayekhi, Jerry A Shields, Carol L Shields

Wills Eye Hospital Papers

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.

Estrogen/Progesterone Receptor And Her2 Discordance Between Primary Tumor And Brain Metastases In Breast Cancer And Its Effect On Treatment And Survival, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Journal Articles

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM).

METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the …

Upregulation Of Cpt1a Is Essential For The Tumor-Promoting Effect Of Adipocytes In Colon Cancer, Xiaopeng Xiong, Yang-An Wen, Rachelle Fairchild, Yekaterina Y. Zaytseva, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient …

The Landscape Of Rna Polymerase Ii-Associated Chromatin Interactions In Prostate Cancer, Susmita G Ramanand, Yong Chen, Jiapei Yuan, Kelly Daescu, Maryou Bk Lambros, Kathleen E Houlahan, Suzanne Carreira, Wei Yuan, Guemhee Baek, Adam Sharp, Alec Paschalis, Mohammed Kanchwala, Yunpeng Gao, Adam Aslam, Nida Safdar, Xiaowei Zhan, Ganesh V Raj, Chao Xing, Paul C Boutros, Johann De Bono, Michael Q Zhang, Ram S Mani

Faculty Scholarship for the College of Science & Mathematics

Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing …

Tumor Boards During Covid-19 Pandemic, Ahmed Nadeem Abbasi

Department of Radiation Oncology

No abstract provided.

Lung Metastasis Postradioembolization Of Hepatocellular Carcinoma With Tumor In Vein, Harit Kapoor, Sreeja Sanampudi, Joseph W. Owen, Driss Raissi

Radiology Faculty Publications

Transarterial radioembolization (TARE) is one of the few treatment options available for infiltrative hepatocellular carcinoma with tumor in vein. This is backed by the published data showing marginally favorable toxicity profile compared with other locoregional and systemic therapies. Although lung shunt fraction studies are performed to prevent radiation injury to the lungs, TARE-induced embolization/metastasis to the lungs has not been reported before. We report an intriguing case of new lung metastases within 1 month after TARE for infiltrative hepatocellular carcinoma with a tumor in the vein, with only a slightly elevated but acceptable lung shunt fraction. This report brings to …

Surgical Resection Of Convexity Meningiomas: A Single Center Retrospective Analysis, Haley Wendt, Michael Baldassari, Donald Ye, Kevin Judy

Phase 1

Introduction: Dural convexity meningiomas (CMs) are the most common primary intracranial tumors. Although surgical resection carries relatively low risk, it is necessary to quantify perioperative risks from a large patient cohort and identify factors contributing to short-term and long-term outcomes.

Methods: Patients who underwent craniotomy for resection of CMs between January 2012-December 2018 at a single large academic center were reviewed for pre-operative demographics, radiographic characteristics, and post-operative outcomes.

Results: 122 cases of CMs were identified. Common presenting symptoms included headache (39.3%), seizure (27.0%) and weakness/paralysis (18%). CMs were located over frontal, parietal, temporal, and occipital lobes in 57.4%, …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

Statistics Of Tumor Micro-Environment, Brenton Maisel, Inna Chervoneva

Phase 1

Introduction: Immune cells play a prominent role in keeping tumors suppressed, but how the distribution of these immune cells within a tumor’s microenvironment remains poorly understood. The long-term goal of this project is to study how statistical spatial distributions of different immune cells is associated with clinical outcome. The first objective is developing an algorithm for identifying different types of immune cells.

Methods: The data motivating this project includes spatial localization information (x-y coordinates) and expression levels of immune cell CD markers quantified by immunofluorescence immunohistochemistry (IF-IHC) in ~1,500 cases of invasive breast cancer. Using expression levels of CD markers …

Hepatocellular Carcinoma Treated With Microwave Ablation Prior To Liver Transplantation, Nicole Wagner, Amanda Smolock, Michael Markovitz, Varun Danda, Christopher Neely, Warren Maley, Jesse Civan, Colette Shaw

Phase 1

Introduction: Ablation is a minimally invasive procedure that limits local liver tumor progression and prolongs patients’ transplantation eligibility. Microwave ablation (MWA) utilizes higher temperatures than the standard of care, radiofrequency ablation (RFA), which increases efficiency. Meta-analyses compared MWA with RFA for the treatment of HCC and showed similar efficacy and safety between these modalities. However, limited pathologic data exists determining whether explanted tumors remained viable after MWA.

Methods: Our database was reviewed retrospectively for patients with HCC who underwent MWA prior to liver transplantation between 2013 and 2019. Patient demographics, etiology of disease, tumor size, procedure details, bilirubin, MELD, …