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GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours
Günter K Stalla1,2, Christina Dimopoulou1,2, Caroline Jung-Sievers3
1Medicover Neuroendocrinology, Munich, Germany.
Abstract:
Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing's disease. In view of the development of additional treatment concepts for the treatment of pituitary adenomas we speculate about the relevance of RSUME as a potential target for the development of an anti-angiogenic therapy. Moreover, the role of BMP-4 which stimulates prolactinoma development through the Smad signalling cascade is described and its role as putative drug target for the treatment of prolactinomas is discussed. Regarding the well-known resistance of a part of somatotropinomas to somatostatin analogue treatment, recently identified mechanisms responsible for the drug resistance are summarized and ways to overcome them in future treatment concepts are presented. Concerning novel therapeutic options for patients with Cushing's disease the impact of retinoic acid, which is currently tested in clinical studies, is shown, and the action and putative therapeutic impact of silibinin to resolve glucocorticoid resistance in these patients is critically discussed.
Insights
Despite effective pituitary tumor treatments, many patients experience incomplete recovery and persistent health issues. This review explores reasons for this discrepancy and discusses novel therapeutic targets like RSUME and BMP-4 for improved patient outcomes.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Established treatments for pituitary tumors include surgery, dopamine agonists, somatostatin analogues, and radiotherapy.
- A significant portion of patients remain incompletely cured due to factors like incomplete resection or drug resistance.
- Even with normalized hormone levels, patients often exhibit persistent metabolic, cardiovascular, or neuropsychiatric comorbidities, impacting quality of life.
Purpose of the Study:
- To discuss reasons for the gap between biochemical cure and incomplete recovery from tumor-associated comorbidities.
- To delineate clinical management strategies for acromegaly and Cushing's disease.
- To explore novel therapeutic targets and concepts for pituitary adenoma treatment.
Main Methods:
- Review of existing literature on pituitary tumor treatment and outcomes.
- Discussion of molecular mechanisms underlying treatment resistance and persistent comorbidities.
- Exploration of potential new therapeutic targets, including RSUME, BMP-4, retinoic acid, and silibinin.
Main Results:
- Reasons for the discrepancy between biochemical cure and persistent comorbidities are discussed.
- Potential therapeutic targets such as RSUME for anti-angiogenic therapy and BMP-4 for prolactinoma treatment are identified.
- Mechanisms of somatostatin analogue resistance in somatotropinomas are summarized, with strategies to overcome them.
- The impact of retinoic acid and silibinin for Cushing's disease treatment resistance is critically evaluated.
Conclusions:
- Addressing persistent comorbidities and treatment resistance is crucial for improving pituitary tumor patient outcomes.
- Novel therapeutic strategies targeting specific molecular pathways offer promise for future treatment paradigms.
- Further research into targets like RSUME, BMP-4, retinoic acid, and silibinin may lead to more effective pituitary adenoma management.
