TERT structural rearrangements in metastatic pheochromocytomas
Pheochromocytomas (PC) and paragangliomas (PGL) are endocrine tumors for which the genetic and clinicopathological features of metastatic progression remain incompletely understood. As a result, the risk of metastasis from a primary tumor cannot be predicted. Early diagnosis of individuals at high risk of developing metastases is clinically important and the identification of new biomarkers that are predictive of metastatic potential is of high value. Activation of TERT has been associated with a number of malignant tumors, including PC/PGL. However, the mechanism of TERT activation in the majority of PC/PGL remains unclea...
Source: Endocrine-Related Cancer - December 18, 2017 Category: Endocrinology Authors: Dwight, T., Flynn, A., Amarasinghe, K., Benn, D. E., Lupat, R., Li, J., Cameron, D. L., Hogg, A., Balachander, S., Candiloro, I. L. M., Wong, S. Q., Robinson, B. G., Papenfuss, A. T., Gill, A. J., Dobrovic, A., Hicks, R. J., Clifton-Bligh, R. J., Tothill, Tags: Research Source Type: research
Endocrine side effects of cancer immunotherapy
Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4...
Source: Endocrine-Related Cancer - November 2, 2017 Category: Endocrinology Authors: Cukier, P., Santini, F. C., Scaranti, M., Hoff, A. O. Tags: Thematic Review Source Type: research
Immune responses in the thyroid cancer microenvironment: making immunotherapy a possible mission
The incidence of thyroid cancers has been steadily increasing worldwide over the past few decades. Although five-year survival rates for differentiated thyroid cancers are upwards of 90%, clinical outcomes for patients with undifferentiated, recurrent and/or metastatic disease are often dismal despite conventional interventions. As such, there is a demand for novel treatment options. Cancer immunotherapy represents the ultimate form of personalized medicine by leveraging the specificity and potency of a patient’s immune system to kill their tumor. The thyroid cancer microenvironment is rich in immunological cells, ma...
Source: Endocrine-Related Cancer - November 2, 2017 Category: Endocrinology Authors: Mould, R. C., van Vloten, J. P., AuYeung, A. W. K., Karimi, K., Bridle, B. W. Tags: Thematic Review Source Type: research
Androgen deprivation and immunotherapy for the treatment of prostate cancer
Prostate cancer is the most common newly diagnosed malignancy in men, and the second most common cause of cancer-related death in the United States. The primary treatment for recurrent prostate cancer is androgen deprivation, and this therapy is typically continued lifelong for patients with metastatic prostate cancer. Androgens and androgen deprivation have profound effects on the immune system, a finding that has become more appreciated in an era where immune-based treatments for cancer are being increasingly explored. Preclinical studies suggest that androgen deprivation could potentially positively or negatively affect...
Source: Endocrine-Related Cancer - November 2, 2017 Category: Endocrinology Authors: Gamat, M., McNeel, D. G. Tags: Thematic Review Source Type: research
The role of the tumour microenvironment in immunotherapy
Recent success in immunomodulating strategies in lung cancer and melanoma has prompted much enthusiasm in their potential to treat other advanced solid malignancies. However, their applications have shown variable success and are even ineffective against some tumours. The efficiency of immunotherapies relies on an immunogenic tumour microenvironment. The current field of cancer immunology has focused on understanding the interaction of cancer and host immune cells to break the state of immune tolerance and explain how molecular patterns of cytokines and chemokines affect tumour progression. Here, we review our current know...
Source: Endocrine-Related Cancer - November 2, 2017 Category: Endocrinology Authors: Gasser, S., Lim, L. H. K., Cheung, F. S. G. Tags: Thematic Review Source Type: research
Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way
We present the challenges and the opportunities of using immune checkpoint inhibitors against these endocrine malignancies, highlighting the breakthroughs and pitfalls that have recently emerged. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - November 2, 2017 Category: Endocrinology Authors: Cunha, L. L., Marcello, M. A., Rocha-Santos, V., Ward, L. S. Tags: Thematic Review Source Type: research
Cancer immunotherapy: unique perspectives for endocrine-related cancers
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - November 2, 2017 Category: Endocrinology Authors: Ngeow, J. Y. Y., Ward, L. S. Tags: Editorials Source Type: research
Sdhd ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype
We report that these mice develop enlarged thyroid glands with follicle hypercellularity and increased proliferation. In vitro, human thyroid cell lines with knockdown of SDHD exhibit an enhanced migratory capability, despite no change in proliferative capacity. Interestingly, these cells acquire stem-like features which are also observed in the mouse tumors. The stem-like characteristics are reversed by α-ketoglutarate, suggesting that SDH-associated tumorigenesis results from dedifferentiation driven by an imbalance in cellular metabolites of the TCA cycle. The results of this study reveal a metabolic vulnerability...
Source: Endocrine-Related Cancer - October 20, 2017 Category: Endocrinology Authors: Ashtekar, A., Huk, D., Magner, A., La Perle, K., Zhang, X., Piruat, J. I., Lopez-Barneo, J., Jhiang, S. M., Kirschner, L. S. Tags: Research Source Type: research
TOP1MT deficiency promotes GC invasion and migration via the enhancements of LDHA expression and aerobic glycolysis
Aerobic glycolysis plays an important role in cancer progression. New target genes regulating cancer aerobic glycolysis must be explored to improve patient prognosis. Mitochondrial topoisomerase I (TOP1MT) deficiency suppresses glucose oxidative metabolism but enhances glycolysis in normal cells. Here, we examined the role of TOP1MT in gastric cancer (GC) and attempted to determine the underlying mechanism. Using in vitro and in vivo experiments and analyzing the clinicopathological characteristics of patients with GC, we found that TOP1MT expression was lower in GC samples than in adjacent nonmalignant tissues. TOP1MT kno...
Source: Endocrine-Related Cancer - October 9, 2017 Category: Endocrinology Authors: Wang, H., Zhou, R., Sun, L., Xia, J., Yang, X., Pan, C., Huang, N., Shi, M., Bin, J., Liao, Y., Liao, W. Tags: Research Source Type: research
Circulating steroid hormone variations throughout different stages of prostate cancer
Steroid hormones play a central role in the maintenance and progression of prostate cancer. The androgen receptor is the primary driver of tumor cell proliferation and is activated by the androgens testosterone and 5α-dihydrotestosterone. Inhibition of this pathway through medical or surgical castration improves survival in the majority of advanced prostate cancer patients. However, conversion of adrenal androgen precursors and alternative steroidogenic pathways have been found to contribute to tumor progression and resistance to treatment. The emergence of highly accurate detection methods allows us to study steroid...
Source: Endocrine-Related Cancer - October 9, 2017 Category: Endocrinology Authors: Snaterse, G., Visser, J. A., Arlt, W., Hofland, J. Tags: Review Source Type: research
Molecular and phenotypic evaluation of a novel germline TMEM127 mutation with an uncommon clinical presentation
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - September 27, 2017 Category: Endocrinology Authors: Deng, Y., Flores, S. K., Cheng, Z., Qin, Y., Schwartz, R. C., Malchoff, C., Dahia, P. L. M. Tags: Research Letter Source Type: research
Dynamic risk stratification in the follow-up of thyroid cancer: what is still to be discovered in 2017?
In conclusion, dynamic risk stratification allows for better prediction of the risk of recurrence in thyroid carcinoma, what has been demonstrated in numerous retrospective analyses. However, the validation of this approach in prospective studies seems to be our task for near future. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - September 19, 2017 Category: Endocrinology Authors: Krajewska, J., Chmielik, E., Jarząb, B. Tags: Review Source Type: research
Role of thyroid hormones in the neoplastic process: an overview
Thyroid hormones (TH) are critical regulators of several physiological processes, which include development, differentiation and growth in virtually all tissues. In past decades, several studies have shown that changes in TH levels caused by thyroid dysfunction, disruption of deiodinases and/or thyroid hormone receptor (TR) expression in tumor cells, influence cell proliferation, differentiation, survival and invasion in a variety of neoplasms in a cell type-specific manner. The function of THs and TRs in neoplastic cell proliferation involves complex mechanisms that seem to be cell specific, exerting effects via genomic a...
Source: Endocrine-Related Cancer - September 19, 2017 Category: Endocrinology Authors: Goemann, I. M., Romitti, M., Meyer, E. L. S., Wajner, S. M., Maia, A. L. Tags: Review Source Type: research
Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy
Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment. Androgen receptor and epidermal growth factor receptor overexpression are recognized mechanisms of endocrin...
Source: Endocrine-Related Cancer - September 19, 2017 Category: Endocrinology Authors: Secreto, G., Muti, P., Sant, M., Meneghini, E., Krogh, V. Tags: Commentary Source Type: research
The future: surgical advances in MEN1 therapeutic approaches and management strategies
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal dominant disorder associated with numerous neuroendocrine tumors (NETs). Recent advances in the management of MEN1 have led to a decrease in mortality due to excess hormones; however, they have also led to an increase in mortality from malignancy, particularly NETs. The main challenges are to localize these tumors, to select those that need therapy because of the risk of aggressive behavior and to select the appropriate therapy associated with minimal morbidity. This must be applied to a hereditary disease with a high risk of recurrence. The overall aim o...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Sadowski, S. M., Cadiot, G., Dansin, E., Goudet, P., Triponez, F. Tags: Thematic Review Source Type: research
