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An Endocrine Society Thematic Issue: Endocrine Neoplasia and Cancer 2021

December 2021

Read our special collection of journal articles, published in 2021, focused on endocrine neoplasia and cancer! Curation of the collection was guided by Altmetric Attention Scores and Featured Article designations.

In Endocrine Reviews, Desai and colleagues review standard-of-care hormonal therapies now available for prostate cancer in its various clinical stages.  Brandi and coauthors discuss discoveries about the genetic and molecular signatures of tumors associated with multiple endocrine neoplasia type 1 that support clinical trials of novel targeted therapies, along with advances in diagnostic tools and surgical approaches. Nölting et al. likewise discuss the “logical next step” of personalized therapy of inoperable or metastatic pheochromocytoma and paraganglioma based on genetic cluster-specific analysis.

In Endocrinology, Craig and associates report that a selective inhibitor of the expression cofactor HDAC6, ACY-241, blocks prolactin-stimulated gene expression involved in breast cancer and has therapeutic efficacy in in vitro and in vivo models of the disease. Piemonte and coauthors discuss the role of centrosome defects in breast cancer, including amplification, structural defects, and loss of primary cilium nucleation; these may instigate the tumor evolution that can lead to poor patient outcomes.  And Massman and colleagues report that the post-translational modification O-GlcNAcylation has a central role in adrenocorticotropic hormone-secreting adenomas’ pathophysiology, including cellular proliferation and hypersecretion.

Writing in JCEM, Chen and associates report findings indicating that newly developed papillary thyroid cancer-derived organoids may be a preclinical model for studying clinical response to anticancer drugs in a personalized way or for developing new therapies. Chatterjee and colleagues report that in trial participants who were overweight and had prediabetes, vitamin D supplementation without selection for vitamin insufficiency did not decrease cancer incidence. Itoh and coauthors find that in a claims database, incidence of colorectal cancer increases with increased fasting plasma glucose levels.

Journal of the Endocrine Society authors Siddiqui and colleagues report the successful use of pasireotide, a second-generation somatostatin receptor ligand, in the treatment of three challenging cases of tumor-induced hypoglycemia. Gambelunghe and coauthors provide a favorable long-term follow-up report on the efficacy of ultrasound-guided laser ablation of benign thyroid nodules.  And lastly, Uslar and associates describe a change in the clinical presentation of paraganglioma and pheochromocytoma over a multi-decadal interval, with a marked increase in incidental cases and milder symptoms. 

Endocrine Reviews

Hormonal Therapy for Prostate Cancer

Kunal Desai, Jeffrey M McManus, Nima Sharifi
Graphical Abstract

Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement.

Multiple Endocrine Neoplasia Type 1: Latest Insights

Maria Luisa Brandi, Sunita K Agarwal, Nancy D Perrier, Kate E Lines, Gerlof D Valk, Rajesh V Thakker
Graphical Abstract

Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics, and molecular biology specialists.

Personalized Management of Pheochromocytoma and Paraganglioma

Svenja Nölting, Nicole Bechmann, David Taieb, Felix Beuschlein, Martin Fassnacht, Matthias Kroiss, Graeme Eisenhofer, Ashley Grossman, Karel Pacak
Graphical Abstract

Pheochromocytomas/paragangliomas are characterized by a unique molecular landscape that allows their assignment to clusters based on underlying genetic alterations. With around 30% to 35% of Caucasian patients showing germline mutations in susceptibility genes, pheochromocytomas/paragangliomas have the highest rate of heritability among all tumors.

Endocrinology

Prolactin Drives a Dynamic STAT5A/HDAC6/HMGN2 Cis-Regulatory Landscape Exploitable in ER+ Breast Cancer

Justin M Craig, Tia H Turner, J Chuck Harrell, Charles V Clevenger
An integrated analysis framework enables interrogation of the STAT5A/HDAC6/HMGN2 cis-regulatory landscape in human breast cancer cells.

The hormone prolactin has been implicated in breast cancer pathogenesis and regulates chromatin engagement by the transcription factor, STAT5A. STAT5A is known to inducibly bind promoters and cis-regulatory elements genome-wide, though the mechanisms by which it exerts specificity and regulation of target gene expression remain enigmatic.

Centrosome Aberrations as Drivers of Chromosomal Instability in Breast Cancer

Katrina M Piemonte, Lindsey J Anstine, Ruth A Keri
Centrosome abnormalities induce CIN in cancer cells.

Chromosomal instability (CIN), or the dynamic change in chromosome number and composition, has been observed in cancer for decades. Recently, this phenomenon has been implicated as facilitating the acquisition of cancer hallmarks and enabling the formation of aggressive disease. Hence, CIN has the potential to serve as a therapeutic target for a wide range of cancers.

O-GlcNAcylation Is Essential for Rapid Pomc Expression and Cell Proliferation in Corticotropic Tumor Cells

Logan J Massman, Michael Pereckas, Nathan T Zwagerman, Stephanie Olivier-Van Stichelen
O-GlcNAcylation of proteins

Pituitary adenomas have a staggering 16.7% lifetime prevalence and can be devastating in many patients because of profound endocrine and neurologic dysfunction. To date, no clear genomic or epigenomic markers correlate with their onset or severity. Herein, we investigate the impact of the O-GlcNAc posttranslational modification in their etiology.

The Journal of Clinical Endocrinology & Metabolism

Organoid Cultures Derived From Patients With Papillary Thyroid Cancer

Dong Chen, Yawen Tan, Zhichao Li, Wujiao Li, Lei Yu, Wei Chen, Yuchen Liu, Lisa Liu, Liangfeng Guo, Weiren Huang, Yongsheng Zhao
Flow diagram of establishment and characterization of PTC organoids

Papillary thyroid cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs.

Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study

Ranee Chatterjee, Paul Fuss, Ellen M Vickery, Erin S LeBlanc, Patricia R Sheehan, Michael R Lewis, Rowena J Dolor, Karen C Johnson, Sangeeta R Kashyap, Jason Nelson, Anastassios G Pittas, D2d Research Group
Flow of participants through the D2dCA study

Observational studies suggest that low vitamin D status may be a risk factor for cancer. In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers.

Fasting Plasma Glucose and Incident Colorectal Cancer: Analysis of a Nationwide Epidemiological Database

Hidetaka Itoh, Hidehiro Kaneko, Akira Okada, Yuichiro Yano, Kojiro Morita, Hikari Seki, Hiroyuki Kiriyama, Tatsuya Kamon, Katsuhito Fujiu, Satoshi Matsuoka, Sunao Nakamura, Nobuaki Michihata, Taisuke Jo, Norifumi Takeda, Hiroyuki Morita, Akira Nishiyama, Koichi Node, Hideo Yasunaga, Issei Komuro
A flowchart defining the sample used in the analyses

Although diabetes mellitus (DM) was reported to be associated with incident colorectal cancer (CRC), the detailed association between fasting plasma glucose (FPG) and incident CRC has not been fully understood. We assessed whether hyperglycemia is associated with a higher risk for CRC.

Journal of the Endocrine Society

Pasireotide: A Novel Treatment for Tumor-Induced Hypoglycemia Due to Insulinoma and Non-Islet Cell Tumor Hypoglycemia

Mahwash Siddiqui, Amy Vora, Sadia Ali, Jessica Abramowitz, Sasan Mirfakhraee
Dexcom G4 Platinum continuous glucose monitor tracings

Tumor-induced hypoglycemia is a serious disorder most commonly caused by insulinoma or non-islet cell tumor hypoglycemia (NICTH). The hypoglycemia can be severe and refractory to conventional therapy, leading to significant morbidity and mortality.

Percutaneous Ultrasound-Guided Laser Ablation of Benign Thyroid Nodules: Results of 10-Year Follow-Up in 171 Patients

Giovanni Gambelunghe, Elisa Stefanetti, Nicola Avenia, Pierpaolo De Feo
Median nodule volume in the overall study population over 10 years of follow-up

Percutaneous, ultrasound-guided laser ablation is effective in nodular thyroid disease. The aim of this study was to evaluate the long-term (10-year) efficacy and safety of laser ablation in the treatment of benign thyroid nodules.

Clinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A 4-Decade Experience

Thomas Uslar, Ignacio F San Francisco, Roberto Olmos, Stefano Macchiavelo, Alvaro Zuñiga, Pablo Rojas, Marcelo Garrido, Alvaro Huete, Gonzalo P Mendez, Ignacio Cortinez, José Tomás Zemelman, Joaquín Cifuentes, Fernando Castro, Daniela Olivari, José Miguel Domínguez, Eugenio Arteaga, Carlos E Fardella, Gloria Valdés, Rodrigo Tagle, Rene Baudrand
Table 1.Patient and surgery characteristics by decade

Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades.

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