Back to Search
Start Over
Aggressive Cushing’s Disease: Molecular Pathology and Its Therapeutic Approach
- Source :
- Frontiers in Endocrinology, Vol 12 (2021), Frontiers in Endocrinology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Cushing’s disease is a syndromic pathological condition caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) mediated by hypercortisolemia. It may have a severe clinical course, including infection, psychiatric disorders, hypercoagulability, and metabolic abnormalities, despite the generally small, nonaggressive nature of the tumors. Up to 20% of ACTHomas show aggressive behavior, which is related to poor surgical outcomes, postsurgical recurrence, serious clinical course, and high mortality. Although several gene variants have been identified in both germline and somatic changes in Cushing’s disease, the pathophysiology of aggressive ACTHomas is poorly understood. In this review, we focused on the aggressiveness of ACTHomas, its pathology, the current status of medical therapy, and future prospects. Crooke’s cell adenoma (CCA), Nelson syndrome, and corticotroph pituitary carcinoma are representative refractory pituitary tumors that secrete superphysiological ACTH. Although clinically asymptomatic, silent corticotroph adenoma is an aggressive ACTH-producing pituitary adenoma. In this review, we summarize the current understanding of the pathophysiology of aggressive ACTHomas, including these tumors, from a molecular point of view based on genetic, pathological, and experimental evidence. The treatment of aggressive ACTHomas is clinically challenging and usually resistant to standard treatment, including surgery, radiotherapy, and established medical therapy (e.g., pasireotide and cabergoline). Temozolomide is the most prescribed pharmaceutical treatment for these tumors. Reports have shown that several treatments for patients with refractory ACTHomas include chemotherapy, such as cyclohexyl-chloroethyl-nitrosourea combined with 5-fluorouracil, or targeted therapies against several molecules including vascular endothelial growth factor receptor, cytotoxic T lymphocyte antigen 4, programmed cell death protein 1 (PD-1), and ligand for PD-1. Genetic and experimental evidence indicates that some possible therapeutic candidates are expected, such as epidermal growth factor receptor tyrosine kinase inhibitor, cyclin-dependent kinase inhibitor, and BRAF inhibitor. The development of novel treatment options for aggressive ACTHomas is an emerging task.
- Subjects :
- Oncology
Vascular Endothelial Growth Factor A
Endocrinology, Diabetes and Metabolism
Review
Ligands
chemistry.chemical_compound
aggressiveness/physiology
0302 clinical medicine
Endocrinology
Cushing’s disease (CD)
Receptors, Somatostatin
Pathology, Molecular
Cushing's disease (CD)
Molecular pathology
Syndrome
targeted therapy
ACTH-Secreting Pituitary Adenoma
Ketoconazole
Dopamine Agonists
Steroids
medicine.drug
Adenoma
medicine.medical_specialty
030209 endocrinology & metabolism
Diseases of the endocrine glands. Clinical endocrinology
Nelson Syndrome
03 medical and health sciences
Adrenocorticotropic Hormone
Pituitary adenoma
Cabergoline
Internal medicine
medicine
Temozolomide
Humans
Pituitary Neoplasms
Pituitary ACTH Hypersecretion
business.industry
Pituitary tumors
Carcinoma
Reproducibility of Results
Cushing's disease
aggressiveness
medicine.disease
RC648-665
Pasireotide
chemistry
physiology
Pituitary carcinoma
medical treatment/surgical treatment
pathology
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 16642392
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Endocrinology
- Accession number :
- edsair.doi.dedup.....a7865e7e1714b8d540d9ef05672033ce