From blocking to targeting: Landmark review charts revolution in hormone treatment

CHICAGO, 3 December 2024 - A comprehensive review published in Brain Medicine today charts the transformative journey of pituitary tumor treatment, from early experiments in hormone regulation to modern precision therapies, while paying tribute to a pioneering figure in neuroendocrinology.

Professor Mark E. Molitch, Emeritus Professor at Northwestern University Feinberg School of Medicine, provides an unprecedented historical perspective on how our understanding of pituitary tumors and their treatment has evolved over seven decades. The review, which honors Dr. Seymour Reichlin's 100^th birthday and his groundbreaking contributions to the field, offers critical insights into both past achievements and future directions in neuroendocrinology.

"Dr. Reichlin's 1963 article in the New England Journal of Medicine strongly influenced many of us to pursue neuroendocrinology from both basic science and clinical medicine aspects," Professor Molitch explains. "The regulation of each pituitary hormone by the hypothalamus was explained in depth, including the concepts that would become critical to the subsequent development of medical treatments for pituitary tumors."

The review tracks the remarkable evolution of treatment approaches across different types of pituitary tumors. For prolactinomas, the most common type of hormone-secreting pituitary adenoma, the development of dopamine agonists marked a revolutionary shift in treatment paradigms. "What began with observations about ergot derivatives in the 1950s led to the development of bromocriptine and later cabergoline, medications that have transformed patient care," Professor Molitch notes.

In the field of acromegaly treatment, the discovery of somatostatin and its receptors opened new therapeutic possibilities. The review details how this finding led to the development of somatostatin receptor ligands (SRLs), which now serve as cornerstone treatments for patients with acromegaly and thyrotropin-secreting adenomas. Recent advances in this area include the development of oral formulations, potentially making treatment more accessible and convenient for patients.

The paper also explores the complex challenges in treating Cushing's disease, where understanding the intricate balance of hormone regulation has led to multiple therapeutic approaches. Professor Molitch discusses how medications like osilodrostat and mifepristone represent significant advances in treatment options, while acknowledging the continuing need for personalized treatment strategies.

"The field has moved from simply blocking hormone production to understanding and targeting specific molecular pathways," Professor Molitch observes. "This evolution has been particularly important in treating aggressive pituitary tumors and carcinomas, where we now have options like temozolomide and various immunotherapies."

The review gives special attention to the treatment of clinically nonfunctioning pituitary adenomas, an area where significant progress has been made in understanding tumor biology and developing targeted interventions. Professor Molitch's analysis suggests that the future may lie in combination therapies that target multiple pathways simultaneously.

This comprehensive overview is particularly meaningful given Professor Molitch's long-standing collaboration with Dr. Reichlin. Their partnership, which resulted in 14 co-authored publications between 1978-1987, helped establish many of the fundamental principles that guide current treatment approaches. "Focus, collaboration, and mutual respect are the ingredients for an exciting scientific journey," Professor Molitch shares, emphasizing the importance of multidisciplinary approaches in modern neuroendocrinology.

Looking to the future, the review identifies several promising areas for continued research, including:

• The development of more selective receptor modulators

• The potential of immunotherapy in treating aggressive tumors

• The role of molecular markers in predicting treatment response

• The optimization of combination therapy approaches

The paper concludes by examining emerging molecular pathways and novel therapeutic targets that may lead to even more effective treatments in the coming years. This forward-looking perspective, grounded in historical understanding, provides valuable insights for both current practitioners and future researchers in the field.

The full peer-reviewed article, titled "Medical therapy of pituitary adenomas," is available in the December 3, 2024 issue of Brain Medicine. The article is freely accessible online at https://doi.org/10.61373/bm024i.0127.

About Brain Medicine: Brain Medicine (ISSN: 2997-2639) is a peer-reviewed journal published by Genomic Press, New York. Brain Medicine is a new home for the cross-disciplinary pathway from innovation in fundamental neuroscience to translational initiatives in brain medicine. The journal’s scope includes the underlying science, causes, outcomes, treatments, and societal impact of brain disorders, across all clinical disciplines and their interface.