Signifor (pasireotide) / Recordati 
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  • ||||||||||  Isturisa (osilodrostat) / Novartis, Recordati
    Osilodrostat in patients with persistent or recurrent Cushing's Disease: a real-life single center experience () -  Oct 1, 2022 - Abstract #ENEA2022ENEA_219;    
    Conclusions Osilodrostat treatment resulted in control of hypercortisolemia in patients unresponsive to previous medical therapies and sustained control but with a better dosing regimen and fewer side-effects in those who were already controlled. Based on our preliminary experience, it seems that osilodrostat is a promising effective and safe choice for the treatment of patients with CD with persistent or recurrent disease.
  • ||||||||||  Signifor (pasireotide) / Recordati
    First-generation somatostatin receptor ligands in the treatment of acromegaly: real-world patient journey (Forum 1) -  Oct 1, 2022 - Abstract #ENEA2022ENEA_117;    
    Results The most common medication class observed was first-generation SRLs (i.e., lanreotide or octreotide; n=381), followed by DAs (n=241), GHRAs (n=109) and second-generation SRLs (i.e., pasireotide; n=11)...Interestingly, most patients did not switch medications after treatment initiation, indicating a degree of inertia in acromegaly treatment choices; patients may therefore achieve the best long‑term outcomes by initiating medications with greater persistence records. Bibliography
  • ||||||||||  Signifor (pasireotide) / Recordati
    Somatostatin and ghrelin systems characterization and therapeutic potential in liver diseases (Forum 1) -  Oct 1, 2022 - Abstract #ENEA2022ENEA_78;    
    Cell proliferation in response to natural (SST/CORT/NST) and synthetic (Lanreotide, Ocreotide, Pasireotide, BIM-23926) peptides was evaluated in human liver cells (cell lines and primary cultures)...In vitro assays revealed a decreased proliferation after treatment with SST, CORT, NST and the synthetic analogues, which was strongly dependent on the expression of the receptors. This study demonstrates an ample alteration of SST/CORT/NST and ghrelin systems in liver pathologies, and suggests the prognostic and therapeutic potential of certain components of these hormonal systems (i.e. GPR107) and of SST-analogues for their clinical management.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Retrospective data, Journal:  Pasireotide treatment in Cushing's disease: A single tertiary center's experience. (Pubmed Central) -  Sep 29, 2022   
    Pasireotide treatment is an alternative treatment in CD, remission is obtained in the first months of treatment, and continues for an extended period. Although hyperglycemia is the most common adverse effect, it can be successfully controlled.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Journal:  Evaluation of PepT1 (SLC15A1) Substrate Characteristics of Therapeutic Cyclic Peptides. (Pubmed Central) -  Aug 27, 2022   
    Although inhibition of Gly-Sar uptake was observed, uptake of octreotide and pasireotide was not increased in SLC15A1 overexpressing cells, indicating a lack of transport by hPepT1. Our data clearly indicate that octreotide and pasireotide are nonsubstrate inhibitors of hPepT1 and that their oral bioavailability cannot be explained by absorption via hPepT1.
  • ||||||||||  Somavert (pegvisomant) / Pfizer, Signifor (pasireotide) / Recordati
    Review, Journal:  Second line treatment of acromegaly: Pasireotide or Pegvisomant? (Pubmed Central) -  Aug 7, 2022   
    According to the high efficacy of these treatments and their molecular mechanisms of action, the choice of second line therapies should be personalized. In this review, we summarize the evidence on clinical, molecular and morphological aspects that may predict the response to second line therapies, in order to integrate and translate in the clinical practice for a patient-tailored therapeutic approach.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Journal:  Somatostatin receptor ligands suppressed proliferation and lipogenesis in 3T3-L1 preadipocytes. (Pubmed Central) -  Aug 5, 2022   
    We found that three SRLs (octreotide, TT232 and pasireotide) inhibited cell viability after 8-48 h but not 4 h...SRLs inhibit the proliferation and lipogenesis in preadipocytes. Their inhibitory effects on cell proliferation may be mediated by the downregulated PI3K/Akt pathway, and the suppressive actions on lipogenesis may be related to the decreased PPARγ and C/EBPα expression.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Preclinical, Journal:  Improved pasireotide response in USP8 mutant corticotroph tumours in vitro. (Pubmed Central) -  Aug 3, 2022   
    The murine Sstr5 promoter has two binding sites for the activating protein 1 (AP-1) and USP8 mutants possibly mediate their action by stimulating AP-1 transcriptional activity. Our data corroborate the USP8 mutational status as a potential marker of pasireotide response and describe a potential mechanism through which USP8 mutants may regulate SSTR5 gene expression.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Clinical, Retrospective data, Review:  Pasireotide-Induced Shrinkage in GH and ACTH Secreting Pituitary Adenoma: A Systematic Review and Meta-Analysis. (Pubmed Central) -  Jul 20, 2022   
    This result strengthens the role of PAS treatment in pituitary adenomas, particularly in those with an invasive behavior, with progressive growth and/or extrasellar extension, with a low likelihood of surgical gross-total removal, or with large postoperative residual tissue. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022328152, identifier CRD42022328152.
  • ||||||||||  Korlym (mifepristone) / Corcept Therap, Signifor (pasireotide) / Recordati, Mifeprex (mifepristone) / Danco Laboratories
    Hedgehog-Induced Somatostatin Receptor Expression is Inhibited by the Activation of the Glucocorticoid Receptor Signaling Pathway in Human Pituitary Adenoma Organoids (ENDOExpo, Pod 4) -  Jul 16, 2022 - Abstract #ENDO2022ENDO_2880;    
    We developed a human pituitary adenoma organoid model from induced pluripotent stem cells treated with the glucocorticoid receptor (GR) antagonist mifepristone, and co-treated them with or without SSTR agonists pasireotide or octreotide...Learning Objective 2: Understand how pituitary organoids are used as preclinical models to identify therapeutic approaches for Cushing's disease. Science Topic(s) for Neuroendocrinology and Pituitary: Pituitary Tumors
  • ||||||||||  Signifor (pasireotide) / Recordati
    Review, Journal:  Pasireotide-a novel somatostatin receptor ligand after 20 years of use. (Pubmed Central) -  Jun 4, 2022   
    This review presents data on the efficacy and safety of pasireotide treatment mostly in patients with acromegaly and Cushing's disease. Moreover, other possible therapeutic applications of pasireotide are mentioned.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Journal:  P720R USP8 Mutation Is Associated with a Better Responsiveness to Pasireotide in ACTH-Secreting PitNETs. (Pubmed Central) -  May 30, 2022   
    In situ Proximity Ligation Assay and immunoflurescence experiments revealed that P720R USP8 mutant is still able to bind 14-3-3 proteins in AtT-20 cells, without affecting SSTR5 localization. In conclusion, P720R USP8 mutation might be considered as a molecular predictor of favourable response to pasireotide in corticotroph tumor cells.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Journal:  Incretin Response to Mixed Meal Challenge in Active Cushing's Disease and after Pasireotide Therapy. (Pubmed Central) -  May 21, 2022   
    No differences in incretin response to MMTT were recorded during PAS therapy. The discrepancy between insulin and glucagon trends while on PAS may be an important pathophysiological mechanism in this iatrogenic DM; hence restoring insulin:glucagon ratio by either enhancing insulin secretion or reducing glucagon tone can be a potential therapeutic target.
  • ||||||||||  Somavert (pegvisomant) / Pfizer, Signifor (pasireotide) / Recordati
    Journal:  Approach to the patient with treatment resistant acromegaly. (Pubmed Central) -  May 20, 2022   
    However, disease activity is not fully controlled in a significant number of patients treated with surgery and/or high-dose first-generation somatostatin receptor ligands (SRLs) monotherapy. In these circumstances, therefore, repeated surgery, second-line medical therapy, and radiotherapy, alone or combined as multimodal therapeutic strategies should be considered, in a patient-centered perspective.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Clinical, Review, Journal:  Pasireotide for Refractory Hypoglycemia in Malignant Insulinoma- Case Report and Review of the Literature. (Pubmed Central) -  May 14, 2022   
    After several ineffective locoregional and systemic therapeutic lines for the secretory disease, the introduction of pasireotide, a second-generation somatostatin analog, provided an improved clinical and secretory evolution both quickly and sustainably, with an excellent safety profile. Pasireotide is an effective and well-tolerated therapy in the treatment of refractory hypoglycemia in metastatic insulinoma.
  • ||||||||||  Signifor (pasireotide) / Recordati, Sutent (sunitinib) / Pfizer
    Retrospective data, Journal:  Target therapies plus somatostatin analogues in NETs: a network meta-analysis. (Pubmed Central) -  Apr 15, 2022   
    The role of pasireotide should be explored in selected subgroups of patients. Last, the combination of everolimus and octreotide appears promising and should be more widely considered in clinical practice.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Journal:  USP8 inhibitor RA-9 reduces ACTH release and cell growth in tumor corticotrophs. (Pubmed Central) -  Apr 15, 2022   
    Pasireotide is the only pituitary-targeted drug approved for adult patients...Altogether, our data demonstrate that RA-9 is efficient in exerting cytotoxic effects and inhibitory actions on cell proliferation and hormone secretion by modulating the expression of pERK1/2, pCREB and p27. Inhibition of USP8 might represent a novel strategy to target both USP8-wild type and USP8-mutated tumors in CD patients.
  • ||||||||||  octreotide chloride FluidCrystal Injection depot (CAM2029) / Novartis, Signifor (pasireotide) / Recordati
    Clinical, Journal:  Combination of pasireotide and octreotide: effects on GH and IGF-I secretion and glucose metabolism in healthy volunteers. (Pubmed Central) -  Mar 24, 2022   
    These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response. Combined low doses of pasireotide LAR (5 mg) and octreotide LAR (10-30 mg) provided greater suppression of IGF-I than either single agent and did not increase blood glucose or incidence of AEs versus either agent alone.
  • ||||||||||  Signifor (pasireotide) / Recordati
    Preclinical, Journal:  Long-term effects of somatostatin analogues in rat GH-secreting pituitary tumor cell lines. (Pubmed Central) -  Mar 23, 2022   
    Combined low doses of pasireotide LAR (5 mg) and octreotide LAR (10-30 mg) provided greater suppression of IGF-I than either single agent and did not increase blood glucose or incidence of AEs versus either agent alone. Long-term incubation with PAS showed a more potent antitumor activity than that reported after OCT in GH3 cells, mainly modulated by a cell cycle perturbation and a relevant induction in apoptosis.
  • ||||||||||  Somavert (pegvisomant) / Pfizer, Signifor (pasireotide) / Recordati
    Clinical, Review, Journal:  Personalized Medical Treatment in Patients with Acromegaly: A Review. (Pubmed Central) -  Mar 9, 2022   
    An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is increasingly important to tailor treatment to patients' unique characteristics as well as preferences, with a goal of personalizing management to achieve high quality outcomes.
  • ||||||||||  Journal:  The future of somatostatin receptor ligands in acromegaly. (Pubmed Central) -  Feb 19, 2022   
    Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile...New formulations of available SRLs, such as oral, subcutaneous depot and nasal octreotide, may improve patients' adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788 and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.
  • ||||||||||  Metopirone (metyrapone) / HRA Pharma
    Retrospective data, Review:  Effectiveness of Medical Treatment of Cushing's Disease: A Systematic Review and Meta-Analysis. (Pubmed Central) -  Feb 15, 2022   
    New therapeutic options should be investigated due to the limited efficacy and tolerability of the currently available medical treatment for patients with Cushing's disease. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, identifier CRD42020205567.
  • ||||||||||  Somavert (pegvisomant) / Pfizer, Signifor (pasireotide) / Recordati
    Journal, HEOR:  Cost-Utility of Acromegaly Pharmacological Treatments in a French Context. (Pubmed Central) -  Feb 15, 2022   
    This medico-economic analysis highlighted the consistency of the efficiency results with the efficacy results assessed in the pivotal trials. However, most recent treatment guidelines recommend an individualized treatment strategy based on the patient and disease profile.