Article
Surgery
Sourat Darabi, David R. Braxton, Burton L. Eisenberg, Michael J. Demeure
Summary: The study showed that next generation sequencing may identify additional treatment options for patients with adrenocortical cancer, with TP53 and CTNNB1 being the most common mutated genes. Potential targets to FDA-approved drugs were found in some cases, but more drug options and more extensive multi-omic sequencing are needed to further advance the treatment.
Article
Medicine, Research & Experimental
Yu-gang Huang, Dan Li, Li Wang, Xiao-min Su, Xian-bin Tang
Summary: The study revealed that CENPF is significantly overexpressed in ACC patients, which is positively correlated with tumor stage and associated with unfavorable overall survival in ACC patients. GSEA analysis suggested that CENPF is mainly involved in regulating the G2/M phase of the cell cycle and the p53 signaling pathway. Experimental findings indicated that the interaction between CENPF and CDK1 facilitates the G2/M phase transition, cell proliferation, and potentially induces a p53-mediated anti-tumor effect in ACC. Additionally, immune infiltration analysis highlighted the potential use of CENPF inhibitors like Cisplatin, Sunitinib, and Etoposide for ACC therapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Oncology
Marco Lo Iacono, Soraya Puglisi, Paola Perotti, Laura Saba, Jessica Petiti, Claudia Giachino, Giuseppe Reimondo, Massimo Terzolo
Summary: Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. It destroys the adrenal cortex, impairs steroidogenesis, and leads to cell death by deregulating cytochromes P450 enzymes, depolarizing mitochondrial membranes, and accumulating free cholesterol. The exact mechanism of mitotane's action is still unclear, and the variability in in vitro experimental conditions could impact the significance of identified molecular mechanisms.
Article
Endocrinology & Metabolism
Alice Boileve, Elise Mathy, Charles Roux, Matthieu Faron, Julien Hadoux, Lambros Tselikas, Abir Al Ghuzlan, Segolene Hescot, Sophie Leboulleux, Thierry de Baere, Livia Lamartina, Frederic Deschamps, Eric Baudin
Summary: This study aimed to evaluate the therapeutic strategy of locoregional treatments (LRT) combined with mitotane in patients with low tumor burden stage IVA adrenocortical carcinoma (ACC). The results suggest that the combination of LRT and mitotane can improve progression-free survival (PFS) and overall survival (OS) in this selected group of patients with ACC. The study also observed a significant number of complete responses in patients receiving mitotane plus LRT, highlighting the potential benefits of this treatment approach.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Marilyne Daher, Jeena Varghese, Stephen K. Gruschkus, Camilo Jimenez, Steven G. Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T. Campbell, Amishi Y. Shah, Miao Zhang, Rahul A. Sheth, Jose A. Karam, Christopher G. Wood, Nancy D. Perrier, Paul H. Graham, Jeffery E. Lee, Mouhammed Amir Habra
Summary: This study reports that the disease burden and clinical outcomes of adrenocortical carcinoma (ACC) have improved over the past two decades. More patients underwent complete surgical resection and received multiple lines of systemic therapy, indicating the importance of these advancements for guiding management strategies.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Anna Calabrese, Soraya Puglisi, Chiara Borin, Vittoria Basile, Paola Perotti, Anna Pia, Paola Berchialla, Marco Volante, Cristian Fiori, Francesco Porpiglia, Andrea Veltri, Giuseppe Reimondo, Massimo Terzolo
Summary: The management of adrenocortical carcinoma (ACC) recurrences remains controversial. In this retrospective analysis, ACC recurrences were found to occur as a single lesion, multiple lesions in a single organ, or affecting multiple organs. Patients with a single lesion recurrence had a better prognosis, suggesting the use of locoregional treatments for ACC recurrence.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Oncology
Michaela Kuhlen, Pascal Mier, Marina Kunstreich, Lienhard Lessel, Dominik Schneider, Ines Brecht, Denis M. Schewe, Michael C. Fruhwald, Peter Vorwerk, Antje Redlich
Summary: Adjuvant treatment with mitotane and chemotherapy is recommended for paediatric advanced and metastatic adrenocortical carcinoma (ACC), but questions regarding indication, dosage, and length of therapy remain. This study found that the duration of mitotane treatment and reaching the drug's target range significantly impacted patient survival.
ENDOCRINE-RELATED CANCER
(2022)
Article
Multidisciplinary Sciences
Priya H. Dedhia, Hemamylammal Sivakumar, Marco A. Rodriguez, Kylie G. Nairon, Joshua M. Zent, Xuguang Zheng, Katie Jones, Liudmila V. Popova, Jennifer L. Leight, Aleksander Skardal
Summary: Adrenocortical carcinoma (ACC) has a poor prognosis due to a lack of new drugs, which is partly attributed to the absence of suitable preclinical models. In this study, a 3D tumor construct platform was successfully generated from an established ACC cell line. The platform showed expression of biomarkers associated with ACC and demonstrated decreased drug sensitivity compared to 2D cell culture. This work represents the first evidence of a 3D tumor constructs platform for ACC, which can be utilized for mechanistic studies and the development of new intervention and therapy targets.
SCIENTIFIC REPORTS
(2023)
Article
Neurosciences
Tushar Kamath, Abdulraouf Abdulraouf, S. J. Burris, Jonah Langlieb, Vahid Gazestani, Naeem M. Nadaf, Karol Balderrama, Charles Vanderburg, Evan Z. Macosko
Summary: In this study, single-cell genomics was used to analyze thousands of human dopamine neurons and identify a unique population susceptible to Parkinson's disease, which was enriched for genetic risk.
NATURE NEUROSCIENCE
(2022)
Article
Oncology
Peter Istvan Turai, Gabor Nyiro, Katalin Borka, Tamas Micsik, Istvan Liko, Attila Patocs, Peter Igaz
Summary: Distinguishing between adrenocortical adenoma and carcinoma is challenging, and additional diagnostic methods are needed. This study investigated the expression profiles of circRNAs in adrenocortical tumors using next-generation sequencing and RT-qPCR validation, and found that circPHC3 is overexpressed in carcinoma and adenoma. This is the first study to investigate circRNAs in adrenocortical tumors, and further research is needed to understand their biological and diagnostic significance.
Article
Endocrinology & Metabolism
Kate M. Warde, Yi Jan Lim, Eduardo Ribes Martinez, Felix Beuschlein, Paula O'Shea, Constanze Hantel, Michael Conall Dennedy
Summary: This study demonstrates that mitotane-induced cytotoxicity in adrenocortical carcinoma (ACC) may be mediated through enhanced breakdown of lipid droplets and activation of lipolysis. Understanding the role of cholesterol and lipids in ACC could provide potential novel therapeutic options, particularly in mitotane-resistant disease.
Review
Pharmacology & Pharmacy
Claudia Rita Corso, Alexandra Acco, Camila Bach, Sandro Jose Ribeiro Bonatto, Bonald Cavalcante de Figueiredo, Lauro Mera de Souza
Summary: Mitotane, the only FDA-approved adrenolytic drug for treating ACC, exerts cytotoxic and anti-secretory effects on tumor tissues and adrenal cells. High doses are often required to achieve therapeutic plasma levels, leading to potential adverse effects. Understanding its pharmacological profile is crucial for enhancing treatment efficacy and developing new drugs with fewer side effects.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Review
Endocrinology & Metabolism
Massimo Terzolo, Martin Fassnacht
Summary: Surgery remains the most important therapeutic option for non-metastatic ACC, with the surgeon's expertise being more important than surgical technique. For patients at low risk of recurrence, active surveillance can spare them from unnecessary adjuvant mitotane treatment, while those at moderate-to-high risk should ideally enroll in the ongoing ADIUVO2 trial. Prospective multicenter trials are needed for long-term improvement of patient care.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Oncology
Marilda Mormando, Edvina Galie, Marta Bianchini, Rosa Lauretta, Giulia Puliani, Antonio Tanzilli, Umberto Anceschi, Giuseppe Simone, Gianluca Petreri, Giuliana Graziano, Andrea Pace, Marialuisa Appetecchia
Summary: This study aims to investigate the relationship between mitotane plasma levels and neurological toxicity. The findings suggest that mitotane values above 18 mg/L are associated with neurophysiological and neuropsychological abnormalities.
FRONTIERS IN ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Li-Hsin Pan, Chueh-Chuan Yen, Chun-Jui Huang, Xin-Ning Ng, Liang-Yu Lin
Summary: This study aimed to characterize patients with adrenocortical carcinoma (ACC) in Taiwan and determine prognostic predictors of overall and progression-free survival. The findings showed that ENSAT stage, large vessel invasion, and mitotane use were significantly associated with overall survival. However, there were no independent predictors of progression-free survival.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Amy Wu, Qiucen Zhang, Guillaume Lambert, Zayar Khin, Robert A. Gatenby, Hyunsung John Kim, Nader Pourmand, Kimberly Bussey, Paul C. W. Davies, James C. Sturm, Robert H. Austin
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Oncology
Siyuan Zheng, Andrew D. Cherniack, Ninad Dewal, Richard A. Moffitt, Ludmila Danilova, Bradley A. Murray, Antonio M. Lerario, Tobias Else, Theo A. Knijnenburg, Giovanni Ciriello, Seungchan Kim, Guillaume Assie, Olena Morozova, Rehan Akbani, Juliann Shih, Katherine A. Hoadley, Toni K. Choueiri, Jens Waldmann, Ozgur Mete, A. Gordon Robertson, Hsin-Ta Wu, Benjamin J. Raphael, Lina Shao, Matthew Meyerson, Michael J. Demeure, Felix Beuschlein, Anthony J. Gill, Stan B. Sidhu, Madson Q. Almeida, Maria C. B. V. Fragoso, Leslie M. Cope, Electron Kebebew, Mouhammed A. Habra, Timothy G. Whitsett, Kimberly J. Bussey, William E. Rainey, Sylvia L. Asa, Jerome Bertherat, Martin Fassnacht, David A. Wheeler, Gary D. Hammer, Thomas J. Giordano, Roel G. W. Verhaak
Article
Multidisciplinary Sciences
Christophe R. Legendre, Michael J. Demeure, Timothy G. Whitsett, Gerald C. Gooden, Kimberly J. Bussey, Sungwon Jung, Tembe Waibhav, Seungchan Kim, Bodour Salhia
Article
Multidisciplinary Sciences
Jia Zeng, Laimonas Kelbauskas, Aida Rezaie, Kristen Lee, Benjamin Ueberroth, Weimin Gao, Dmitry Derkach, Thai Tran, Dean Smith, Kimberly J. Bussey, Deirdre R. Meldrum
SCIENTIFIC REPORTS
(2016)
Article
Multidisciplinary Sciences
Vivek Nandakumar, Nanna Hansen, Honor L. Glenn, Jessica H. Han, Stephanie Helland, Kathryn Hernandez, Patti Senechal, Roger H. Johnson, Kimberly J. Bussey, Deirdre R. Meldrum
Scientific Reports
(2016)
Article
Multidisciplinary Sciences
Luis Cisneros, Kimberly J. Bussey, Adam J. Orr, Milica Miocevic, Charles H. Lineweaver, Paul Davies
Article
Clinical Neurology
Madhavi Chakravadhanula, Waibhav Tembe, Christophe Legendre, David Carpentieri, Winnie S. Liang, Kimberly J. Bussey, John Carpten, Michael E. Berens, Ratan D. Bhardwaj
JOURNAL OF CHILD NEUROLOGY
(2014)
Editorial Material
Pharmacology & Pharmacy
Aditi A. Bapat, Michael J. Demeure, Kimberly J. Bussey
Article
Multidisciplinary Sciences
Meenu Jain, Lisa Zhang, Myriem Boufraqech, Yi Liu-Chittenden, Kimberly Bussey, Michael J. Demeure, Xiaolin Wu, Ling Su, Karel Pacak, Constantine A. Stratakis, Electron Kebebew
Article
Surgery
Michael J. Demeure, Kathryn E. Coan, Clive S. Grant, Richard A. Komorowski, Elizabeth Stephan, Shripad Sinari, David Mount, Kimberly J. Bussey
Article
Surgery
Michael J. Demeure, Meraj Aziz, Richard Rosenberg, Steven D. Gurley, Kimberly J. Bussey, John D. Carpten
WORLD JOURNAL OF SURGERY
(2014)
Article
Multidisciplinary Sciences
Laimonas Kelbauskas, Honor Glenn, Clifford Anderson, Jacob Messner, Kristen B. Lee, Ganquan Song, Jeff Houkal, Fengyu Su, Liqiang Zhang, Yanqing Tian, Hong Wang, Kimberly Bussey, Roger H. Johnson, Deirdre R. Meldrum
SCIENTIFIC REPORTS
(2017)
Article
Veterinary Sciences
Robert F. Oldt, Kimberly J. Bussey, Matthew L. Settles, Joseph N. Fass, Jeffrey A. Roberts, J. Rachel Reader, Srivathsan Komandoor, Victor A. Abrich, Sreetharan Kanthaswamy
COMPARATIVE MEDICINE
(2020)
Review
Biochemistry & Molecular Biology
Kimberly J. Bussey, Paul C. W. Davies
Summary: Cancer initiation and progression may represent a systematic reversion to simpler ancestral phenotypes in response to stress, a concept known as the atavism theory. Research has shown that cancer cells tend to over-express evolutionary older genes and rewire the architecture linking unicellular and multicellular gene networks. Some cancer hallmarks, such as the elevated mutation rate, may be driven by ancient homologs of SOS genes, activated in stressed bacteria for biological workarounds.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Oncology
Kimberly J. Bussey, Aditi Bapat, Claire Linnehan, Melissa Wandoloski, Erica Dastrup, Erik Rogers, Paul Gonzales, Michael J. Demeure
CLINICAL AND TRANSLATIONAL MEDICINE
(2016)