New HIF2{alpha} inhibitors: potential implications as therapeutics for advanced pheochromocytomas and paragangliomas
Two recent independent studies published in Nature show robust responses of clear cell renal cell carcinoma (ccRCC) cell lines, preclinical ccRCC xenograft models and, remarkably, a patient with progressive ccRCC despite receiving multiple lines of treatment, to the long-awaited, recently developed inhibitors of hypoxia-inducible factor 2-alpha (HIF2α). This commentary published in Endocrine-Related Cancer is based on the recognition of similar molecular drivers in ccRCC and the endocrine neoplasias pheochromocytomas and paragangliomas (PPGLs), ultimately leading to stabilization of HIFs. HIF-stabilizing mutations ha...
Source: Endocrine-Related Cancer - August 7, 2017 Category: Endocrinology Authors: Toledo, R. A. Tags: Commentary Source Type: research

Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF
Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent repor...
Source: Endocrine-Related Cancer - July 31, 2017 Category: Endocrinology Authors: Imruetaicharoenchoke, W., Fletcher, A., Lu, W., Watkins, R. J., Modasia, B., Poole, V. L., Nieto, H. R., Thompson, R. J., Boelaert, K., Read, M. L., Smith, V. E., McCabe, C. J. Tags: Research Source Type: research

Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas
Pituitary adenomas (PA) represent the largest group of intracranial neoplasms and yet the molecular mechanisms driving this disease remain largely unknown. The aim of this study was to use a high-throughput screening method to identify molecular pathways that may be playing a significant and consistent role in PA. RNA profiling using microarrays on eight local PAs identified the aryl hydrocarbon receptor (AHR) signalling pathway as a key canonical pathway downregulated in all PA types. This was confirmed by real-time PCR in 31 tumours. The AHR has been shown to regulate cell cycle progression in various cell types; however...
Source: Endocrine-Related Cancer - July 24, 2017 Category: Endocrinology Authors: Formosa, R., Borg, J., Vassallo, J. Tags: Research Source Type: research

A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations...
Source: Endocrine-Related Cancer - July 24, 2017 Category: Endocrinology Authors: Dumanski, J. P., Rasi, C., Bjorklund, P., Davies, H., Ali, A. S., Gronberg, M., Welin, S., Sorbye, H., Gronbaek, H., Cunningham, J. L., Forsberg, L. A., Lind, L., Ingelsson, E., Stalberg, P., Hellman, P., Tiensuu Janson, E. Tags: Research Source Type: research

Estradiol for the mitigation of adverse effects of androgen deprivation therapy
Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. Conventional endocrine treatment for PCa leads to global sex steroid deprivation. The ensuing severe hypogonadism is associated with well-documented adverse effects. Recently, it has become apparent that many of the biological actions attributed to androgens in men are in fact not direct, but mediated by estradiol. Available evidence supports a primary role for estradiol in vasomotor stability, skeletal maturation and maintenance, and prevention of fat accumulation. Hence there has been interest in revisiting estradiol as a treatment for PCa. Potent...
Source: Endocrine-Related Cancer - July 24, 2017 Category: Endocrinology Authors: Russell, N., Cheung, A., Grossmann, M. Tags: Review Source Type: research

STAT3 activation by leptin receptor is essential for TNBC stem cell maintenance
Leptin (LEP) binds to the long form of the leptin receptor (LEPRb), leading to the activation of multiple signaling pathways that are potential targets for disrupting the obesity–breast cancer link. In triple-negative breast cancer (TNBC), LEP is hypothesized to predominantly mediate its tumorigenic effects via a subpopulation of LEPRb-positive tumor cells termed cancer stem cells (CSCs) that can initiate tumors and induce tumor progression. Previously, we showed that LEP promotes CSC survival in vivo. Moreover, silencing LEPRb in TNBC cells compromised the CSC state. The mechanisms by which LEPRb regulates TNBC CSC ...
Source: Endocrine-Related Cancer - July 20, 2017 Category: Endocrinology Authors: Thiagarajan, P. S., Zheng, Q., Bhagrath, M., Mulkearns-Hubert, E. E., Myers, M. G., Lathia, J. D., Reizes, O. Tags: Research Source Type: research

A case of a metastatic SDHA mutated paraganglioma re-presenting twenty-three years after initial surgery
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - July 20, 2017 Category: Endocrinology Authors: Casey, R. T., Challis, B. G., Marker, A., Pitfield, D., Cheow, H. K., Shaw, A., Park, S.-M., Simpson, H. L., Maher, E. R. Tags: Letter to the Editor Source Type: research

The penetrance of MEN2 pheochromocytoma is not only determined by RET mutations
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - July 20, 2017 Category: Endocrinology Authors: Castinetti, F., Maia, A. L., Peczkowska, M., Barontini, M., Hasse-Lazar, K., Links, T. P., Toledo, R. A., Dvorakova, S., Mian, C., Bugalho, M. J., Zovato, S., Alevizaki, M., Kvachenyuk, A., Bausch, B., Loli, P., Bergmann, S. R., Patocs, A., Pfeifer, M., C Tags: Research Letter Source Type: research

Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms
Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case–control study was conducted to examine the association of sele...
Source: Endocrine-Related Cancer - July 17, 2017 Category: Endocrinology Authors: Valente, R., Hayes, A. J., Haugvik, S.-P., Hedenstrom, P., Siuka, D., Korsaeth, E., Kammerer, D., Robinson, S. M., Maisonneuve, P., Delle Fave, G., Lindkvist, B., Capurso, G. Tags: Research Source Type: research

Rationale for the development of alternative forms of androgen deprivation therapy
With few exceptions, the almost 30,000 prostate cancer deaths annually in the United States are due to failure of androgen deprivation therapy. Androgen deprivation therapy prevents ligand-activation of the androgen receptor. Despite initial remission after androgen deprivation therapy, prostate cancer almost invariably progresses while continuing to rely on androgen receptor action. Androgen receptor’s transcriptional output, which ultimately controls prostate cancer behavior, is an alternative therapeutic target, but its molecular regulation is poorly understood. Recent insights in the molecular mechanisms by which...
Source: Endocrine-Related Cancer - July 17, 2017 Category: Endocrinology Authors: Kumari, S., Senapati, D., Heemers, H. V. Tags: Review Source Type: research

Testicular vs adrenal sources of hydroxy-androgens in prostate cancer
In this study, we aimed to evaluate the efficiency of serum hydroxy-androgen suppression in patients with localized high-risk prostate cancer under NADT (leuprolide acetate plus abiraterone acetate and prednisone) and interrogate the primary sources of circulating hydroxy-androgens using our recently described stable isotope dilution liquid chromatography mass spectrometric method. For the first time, three androgen diols including 5-androstene-3β,17β-diol (5-adiol), 5α-androstane-3α,17β-diol (3α-adiol), 5α-androstane-3β,17β-diol (3β-adiol), the glucuronide or sulfate c...
Source: Endocrine-Related Cancer - July 6, 2017 Category: Endocrinology Authors: Zang, T., Taplin, M.-E., Tamae, D., Xie, W., Mesaros, C., Zhang, Z., Bubley, G., Montgomery, B., Balk, S. P., Mostaghel, E. A., Blair, I. A., Penning, T. M. Tags: Research Source Type: research

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushings disease
The CABLES1 cell cycle regulator participates in the adrenal–pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing’s disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 ...
Source: Endocrine-Related Cancer - July 6, 2017 Category: Endocrinology Authors: Hernandez-Ramirez, L. C., Gam, R., Valdes, N., Lodish, M. B., Pankratz, N., Balsalobre, A., Gauthier, Y., Faucz, F. R., Trivellin, G., Chittiboina, P., Lane, J., Kay, D. M., Dimopoulos, A., Gaillard, S., Neou, M., Bertherat, J., Assie, G., Villa, C., Mill Tags: Research Source Type: research

KIF1B and NF1 are the most frequently mutated genes in paraganglioma and pheochromocytoma tumors
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - July 6, 2017 Category: Endocrinology Authors: Evenepoel, L., Helaers, R., Vroonen, L., Aydin, S., Hamoir, M., Maiter, D., Vikkula, M., Persu, A. Tags: Research Letter Source Type: research

SDHB mutation carriers with malignant pheochromocytoma respond better to CVD
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - July 6, 2017 Category: Endocrinology Authors: Fishbein, L., Ben-Maimon, S., Keefe, S., Cengel, K., Pryma, D. A., Loaiza-Bonilla, A., Fraker, D. L., Nathanson, K. L., Cohen, D. L. Tags: Research Letter Source Type: research

Effect of hormone secretory syndromes on neuroendocrine tumor prognosis
The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones. This has been reduced with several drugs: proton-pump inhibitors decrease...
Source: Endocrine-Related Cancer - July 4, 2017 Category: Endocrinology Authors: Zandee, W. T., Kamp, K., van Adrichem, R. C., Feelders, R. A., de Herder, W. W. Tags: Review Source Type: research