Emerging drugs for the treatment of acromegaly

Campana, Claudia; Corica, Giuliana; Nista, Federica; Cocchiara, Francesco; Graziani, Giulia; Khorrami, Keyvan; Franco, Marta; Boschetti, Mara; Ferone, Diego; Gatto, Federico

doi:10.1080/14728214.2020.1819983

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…Traditional pharmacological treatments include somatostatin analogs (SSA), growth hormone receptor antagonists (GHRA), and dopamine receptor agonists (DA). However, the e cacy of these drugs is limited, as evidenced by the low remission rate (10-35%), high resistance rate (25-50%), and high cost [13][14][15][16][17][18][19]. Radiotherapy is usually reserved as a third-line option [5,7] due to its many potential complications such as hypopituitarism and vision loss [20,21].…”

Section: Introductionmentioning

confidence: 99%

Targeting RACGAP1 Suppresses Growth Hormone Pituitary Adenoma Growth

Sun,

Ji,

Zhou

et al. 2024

Preprint

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Purpose: Growth hormone pituitary adenoma (GHPA) is a major subtype of pituitary adenoma (PA), with tumor enlargement and abnormal secretion of growth hormone (GH) often causing complications. Rac GTPase-activating protein 1 (RACGAP1), a member of the guanine triphosphatase-activating protein family, is highly overexpressed in multiple tumors and promotes tumor growth. However, the role of RACGAP1 in GHPA remains unelucidated. Besides, specific inhibitors targeting RACGAP1 have not yet been developed. In this study, we aimed to determine the expression and function of RACGAP1 in GHPA and identify effective inhibitors against RACGAP1. Methods: Immunohistochemistry was used to detect the expression of RACGAP1 in GHPA and normal pituitary tissues. The effect of RACGAP1 on cell proliferation, apoptosis, and cell cycle was evaluated by knockdown of RACGAP1 in GH3 cells in vitro and xenograft models of GHPA in vivo. The downstream mechanism of RACGAP1 was explored by RNA sequencing, bioinformatic analysis, and Western blot. Inhibitors targeting RACGAP1 were screened and verified through a structure-based virtual docking method, cell viability assays, and surface plasmon resonance (SPR) experiments. Results: RACGAP1 expression was increased in GHPA compared with normal pituitary tissues. Knocking down RACGAP1 suppressed cell growth in vitro and in vivo. Preliminary mechanism studies indicated that inhibition of RACGAP1 led to the upregulation of p21 and the downregulation of several genes involved in the cell cycle signaling pathway, such as Cyclin A, CDK1, and CDK2. Moreover, DB07268 was identified for the first time as an effective RACGAP1 inhibitor that could prominently restrain the proliferation of GH3 cells. Conclusion: This study demonstrates that RACGAP1 plays a critical role in GHPA, highlighting the novel inhibitor DB07268 as a promising therapeutic approach.

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Section: Introductionmentioning

confidence: 99%

Targeting RACGAP1 Suppresses Growth Hormone Pituitary Adenoma Growth

Sun,

Ji,

Zhou

et al. 2024

Preprint

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“…Medical therapies such as somatostatin receptor ligands (SRLs), cabergoline, and pegvisomant may be recommended for patients with persistent acromegaly after surgery. Radiotherapy is another possible option for management and may be utilized when surgery is not feasible or when surgery and medications have not been successful in controlling excess GH production [9,[11][12][13]. Firstgeneration SRLs -octreotide acetate, octreotide long-acting release (LAR), lanreotide depot, oral octreotide, and second-generation SRLs (pasireotide LAR) activate distinct subsets of somatostatin receptors (SSTRs).…”

Section: Introductionmentioning

confidence: 99%

Coexistence of acromegaly and pancreatic adenocarcinoma — case study

Grzelak,

Rosiek,

Kos-Kudła

2024

Medical Research Journal

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Acromegaly is a rare condition characterized by increased secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). This disease may predispose to the development of neoplasms. This study aims to present a case of a patient with acromegaly and coexisting pancreatic adenocarcinoma and to highlight the potential positive impact of somatostatin receptor ligands used in acromegaly treatment on the potential benefits when combined with conventional pancreatic adenocarcinoma therapy.

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“…In certain rare clinical scenarios, Computed tomography (CT) scan of the thorax and abdomen is done to localize towards an ectopic source of secretion of GH or growth hormone-releasing hormone (GHRH) [10]. Even though transsphenoidal surgery is considered the mainstay of therapy, medical management with drugs like octreotide (somatostatin analog), cabergoline (dopamine agonists), pegvisomant (GH receptor antagonist) has been shown to help keep IGF-1 levels in the normal range [11][12][13]. Acromegaly is a complex disorder that manifests with multiple system involvement, out of which cardiovascular complications (congestive heart failure) are the main culprit behind the mortality in these patients [14].…”

Section: Introductionmentioning

confidence: 99%

Acromegaly and the Colon: Scoping Beyond the Pituitary

Patel¹,

Grossmann²,

Rodriguez³

et al. 2021

Cureus

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Acromegaly is a complex endocrinological disorder commonly caused by hypersecretion of growth hormone (GH) typically due to pituitary gland tumors. Patients with acromegaly who are successfully treated and biochemically managed have a reasonably average life expectancy. However, it causes a cascade of multisystemic involvement throughout the patient's life, including cardiovascular, neuropsychiatric, respiratory, metabolic, neurological, neoplastic, and gastrointestinal involvement, resulting in a higher rate of hospitalization, lower quality of life, and a shorter life expectancy. Although cardiovascular complications are the primary cause of death in patients with acromegaly, malignancy is now emerging as a major killer in these individuals. Colorectal carcinoma has been reported to be prevalent in acromegaly individuals. This review article has compiled studies to demonstrate a link between acromegaly and colorectal neoplasia, intending to provide a strong foundation for their clinical relationship. This article has summarised a potential pathogenic mechanism and provided insights into the clinical presentation of such patients. Furthermore, this article has provided a brief overview of current screening recommendations for colorectal neoplasia in acromegaly patients.

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Emerging drugs for the treatment of acromegaly

Cited by 4 publications

References 57 publications

Targeting RACGAP1 Suppresses Growth Hormone Pituitary Adenoma Growth

Targeting RACGAP1 Suppresses Growth Hormone Pituitary Adenoma Growth

Coexistence of acromegaly and pancreatic adenocarcinoma — case study

Acromegaly and the Colon: Scoping Beyond the Pituitary

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