^
1m
Pituitary gigantism due to a novel AIP germline splice-site variant. (PubMed, Endocr Oncol)
Pasireotide was therefore prescribed, and afterward cabergoline was added on. IGF-I concentrations decreased but did not normalize. We discovered a novel germline single nucleotide variant in the splicing donor region of intron 2 of the AIP gene (NM_003977.4:c.279+1 G>A), classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines.
Journal
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SSTR (Somatostatin Receptor) • IGF1 (Insulin-like growth factor 1) • SSTR2 (Somatostatin Receptor 2) • SSTR5 (Somatostatin Receptor 5)
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Signifor (pasireotide)
1m
Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3. (PubMed, Proc Natl Acad Sci U S A)
Here, we report four cryoelectron microscopy structures of Gi-coupled SSTR1 and SSTR3 activated by distinct agonists, including the FDA-approved panagonist pasireotide as well as their selective small molecule agonists L-797591 and L-796778...Together with mutagenesis analyses, our structures further reveal the dynamic feature of ligand binding pockets in SSTR1 and SSTR3 to accommodate divergent agonists, the key determinants of ligand selectivity lying across the orthosteric pocket of different SSTR subtypes, as well as the molecular mechanism underlying diversity and conservation of receptor activation. Our work provides a framework for rational design of subtype-selective SSTR ligands and may facilitate drug development efforts targeting SSTRs with improved therapeutic efficacy and reduced side effects.
Journal
|
SSTR (Somatostatin Receptor)
|
Signifor (pasireotide)
1m
Genomic and transcriptomic features of androgen receptor signaling inhibitor resistance in metastatic castration-resistant prostate cancer. (PubMed, J Clin Invest)
We found that patients with SSTR1-low mCRPC tumors derived less benefit from subsequent ARSI therapy in a retrospective cohort. We showed that SSTR1 was antiproliferative in 22Rv1 cells and that the FDA-approved drug pasireotide suppressed 22Rv1 cell proliferation.CONCLUSIONOur findings expand the knowledge of ARSI resistance and point out actionable next steps, exemplified by potentially targeting SSTR1, to improve patient outcomes.FUNDINGNational Cancer Institute (NCI), NIH; Prostate Cancer Foundation; Conquer Cancer, American Society of Clinical Oncology Foundation; UCSF Benioff Initiative for Prostate Cancer Research; Netherlands Cancer Institute.
Journal • Metastases
|
SSTR (Somatostatin Receptor)
|
Signifor (pasireotide)
2ms
Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias. (PubMed, Curr Issues Mol Biol)
On the other hand, a number of somatostatin antagonists may prove useful in certain medical settings, based on their differential affinity for SSTRs. The aim of this review is to present in detail the principal characteristics of all five SSTRs and to provide an overview of the associated therapeutic potential in neoplasias.
Review • Journal
|
SSTR (Somatostatin Receptor)
|
Signifor (pasireotide)
2ms
New trial
|
IGF1 (Insulin-like growth factor 1)
|
Signifor (pasireotide)
3ms
Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin. (PubMed, Int J Mol Sci)
Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.
Retrospective data • Journal
|
CDH1 (Cadherin 1) • SSTR (Somatostatin Receptor) • IGF1 (Insulin-like growth factor 1) • SSTR2 (Somatostatin Receptor 2) • SSTR5 (Somatostatin Receptor 5)
|
Signifor (pasireotide)
3ms
Enrollment open
|
octreotide acetate
3ms
212-Pb-VMT: Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors (clinicaltrials.gov)
P1/2, N=280, Recruiting, Perspective Therapeutics | N=52 --> 280 | Trial completion date: Jan 2028 --> Dec 2029 | Trial primary completion date: Sep 2026 --> Nov 2029
Enrollment change • Trial completion date • Trial primary completion date • Metastases
|
SSTR (Somatostatin Receptor) • CD4 (CD4 Molecule) • SSTR2 (Somatostatin Receptor 2)
|
VMT-𝛼-NET
3ms
POSITANO: A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD (clinicaltrials.gov)
P2/3, N=71, Active, not recruiting, Camurus AB | Trial completion date: Aug 2025 --> Aug 2027
Trial completion date
|
Oclaiz (octreotide subcutaneous depot)
3ms
Medical treatment of acromegaly - When the tumor size matters: A narrative review. (PubMed, Growth Horm IGF Res)
Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).
Review • Journal
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SSTR (Somatostatin Receptor) • IGF1 (Insulin-like growth factor 1)
|
Somatuline Depot (lanreotide prolonged-release subcutaneous) • Signifor LAR (pasireotide long acting release) • octreotide acetate
3ms
Structure and Function of Somatostatin and its Receptors in Endocrinology. (PubMed, Endocr Rev)
Somatostatin analogs, such as octreotide (OCT), lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly...The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies.
Journal
|
SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)
|
Signifor (pasireotide)
4ms
Clinical Evaluation of Response to Octreotide and Chemotherapy in High-Grade Malignant Neuroendocrine Tumors and Promising In Vitro Preclinical Results with Pasireotide. (PubMed, Medicina (Kaunas))
Interestingly, while octreotide did not modify H69 cell proliferation, a strong inhibition of proliferation was detected with the use of pasireotide. In view of these results, a clinical trial in NET G3 and NEC patients using pasireotide is necessary to determine the usefulness of this drug in improving patient treatment.
Preclinical • Journal
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SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2) • SSTR5 (Somatostatin Receptor 5)
|
Signifor (pasireotide)
4ms
Lanreotide versus placebo for tumour reduction in patients with a 68Ga-DOTATATE PET-positive, clinically non-functioning pituitary macroadenoma (GALANT study): a randomised, multicentre, phase 3 trial with blinded outcome assessment. (PubMed, Lancet Reg Health Eur)
A predefined sample of 44 patients with PET-positive NFPMA were randomly assigned (1:1) to lanreotide acetate 120 mg or placebo, both administered as deep subcutaneous injections every 28 days for 72 weeks...Compared with placebo, lanreotide treatment did not reduce tumour size or growth in patients with 68Ga-DOTATATE PET-positive NFPMA. Ipsen Farmaceutica BV.
P3 data • Journal
|
SSTR (Somatostatin Receptor)
|
Somatuline Depot (lanreotide prolonged-release subcutaneous)
4ms
Effects of Sandostatin LAR® in Acromegaly (clinicaltrials.gov)
P4, N=21, Completed, Columbia University | Unknown status --> Completed
Trial completion
|
IGF1 (Insulin-like growth factor 1)
|
octreotide acetate
4ms
A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs (clinicaltrials.gov)
P3, N=196, Active, not recruiting, Sinotau Pharmaceutical Group | Recruiting --> Active, not recruiting
Enrollment closed
|
Lutathera (lutetium Lu 177 dotatate) • octreotide acetate
4ms
New P2 trial
|
octreotide acetate
4ms
Lead-203 VMT-α-Neuroendocrine Tumor Scintigraphy: A Promising Theranostics Agent. (PubMed, Indian J Nucl Med)
As Pb-203 presents an accurate diagnostic surrogate to Pb-212, imaging with Pb-203-labelled peptides can be an important prerequisite to assess the feasibility of TAT with Pb-212-labelled agents. Here, we present the imaging data of a patient with metastatic NET with Pb-203 VMT-α-NET, a somatostatin receptor targeting agent, and demonstrate the matching distribution of Pb-203 VMT-α-NET with Ga-68 DOTANOC.
Journal
|
SSTR (Somatostatin Receptor)
|
VMT-𝛼-NET
4ms
Cabozantinib and Lanreotide as Treatment for Gastroenteropancreatic Neuroendocrine Tumors (clinicaltrials.gov)
P1/2, N=49, Recruiting, National Health Research Institutes, Taiwan | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Aug 2026
Trial completion date • Trial primary completion date • Metastases
|
Cabometyx (cabozantinib tablet) • Somatuline Depot (lanreotide prolonged-release subcutaneous)
5ms
Structural insights into somatostatin receptor 5 bound with cyclic peptides. (PubMed, Acta Pharmacol Sin)
Two cyclic SST analog peptides (pasireotide and octreotide) both can activate SSTR5 and SSTR2...Moreover, we find that the Q2.63, N6.55, F7.35 and ECL2 of SSTR2 play a crucial role in octreotide biased binding of SSTR2. Our results will provide structural insights and offer new opportunities for the drug discovery of better selective pharmaceuticals targeting specific SSTR subtypes.
Journal
|
SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2) • SSTR5 (Somatostatin Receptor 5)
|
Signifor (pasireotide)
5ms
Treatment of Advanced BP-NETS with Lanreotide Autogel/Depot vs Placebo: the Phase III SPINET Study. (PubMed, Endocr Relat Cancer)
Patients' quality of life did not deteriorate and LAN was well tolerated. Although recruitment stopped early and the predefined sample size was not met, SPINET is the largest prospective study to date of SSA therapy in SSTR positive TCs and ACs and suggests clinical benefit in TCs.
P3 data • Journal • Metastases
|
SSTR (Somatostatin Receptor)
|
Somatuline Depot (lanreotide prolonged-release subcutaneous)
5ms
Successful management of a multiple endocrine neoplasia type 1-associated thymic neuroendocrine neoplasms with acute chest pain as initial symptom: A rare case report. (PubMed, Clin Case Rep)
Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6-month follow-up. Thus, acute chest pain can be the first manifestation of MEN1-associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1-associated NEN.
Journal
|
NCAM1 (Neural cell adhesion molecule 1) • MEN1 (Menin 1)
|
octreotide acetate
5ms
New P2 trial
|
Signifor (pasireotide)
5ms
Targeted analysis of Ubiquitin-Specific Peptidase (USP8) in a population of Iranian people with Cushing's disease and a systematic review of the literature. (PubMed, BMC Endocr Disord)
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Review • Journal
|
EGFR (Epidermal growth factor receptor)
|
gefitinib • lapatinib
5ms
Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE). (PubMed, Pituitary)
Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed.
Journal
|
SSTR (Somatostatin Receptor)
|
Signifor (pasireotide)
5ms
Trial completion
|
Signifor (pasireotide)
6ms
Long-term pasireotide-LAR treatment in the personalized therapy of patients with complex acromegaly: a collection of clinical experiences. (PubMed, Drugs Context)
Pasireotide-LAR allowed the normalization of insulin-like growth factor 1 (IGF1) values in all patients and reduced tumour residue volume where present. A good safety profile and long-term tolerability were also reported.
Journal
|
IGF1 (Insulin-like growth factor 1)
|
Signifor LAR (pasireotide long acting release)
6ms
Insights from an Italian Delphi panel: exploring resistance to first-generation somatostatin receptor ligands and guiding second-line medical therapies in acromegaly management. (PubMed, J Endocrinol Invest)
The experts agreed on a holistic management approach to acromegaly. It is therefore necessary to choose currently available highly effective second-line medical treatment (pegvisomant and pasireotide) based on the characteristics of the patients.
Journal
|
SSTR (Somatostatin Receptor) • IGF1 (Insulin-like growth factor 1)
|
Signifor (pasireotide)
7ms
Lutathera in People With Gastroenteropancreatic (GEP), Bronchial or Unknown Primary Neuroendocrine Tumors That Have Spread to the Liver (clinicaltrials.gov)
P1, N=10, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
|
SSTR (Somatostatin Receptor)
|
SSTR positive • SSTR Expression
|
Lutathera (lutetium Lu 177 dotatate)
7ms
Lutathera in People With Gastroenteropancreatic (GEP), Bronchial or Unknown Primary Neuroendocrine Tumors That Have Spread to the Liver (clinicaltrials.gov)
P1, N=10, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
Trial completion date • Trial primary completion date • Metastases
|
SSTR (Somatostatin Receptor)
|
SSTR positive • SSTR Expression
|
Lutathera (lutetium Lu 177 dotatate)
7ms
Lanreotide Autogel Treatment of Patients With Congenital Hyperinsulinism of Infancy (clinicaltrials.gov)
P4, N=3, Completed, Sheba Medical Center | Unknown status --> Completed | N=10 --> 3
Trial completion • Enrollment change
|
Somatuline Depot (lanreotide prolonged-release subcutaneous)
7ms
The Novel SSTR3 Agonist ITF2984 Exerts Antimitotic and Proapoptotic Effects in Human Non-Functioning Pituitary Neuroendocrine Tumor (NF-PitNET) Cells. (PubMed, Int J Mol Sci)
We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.
Journal
|
SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2) • SSTR5 (Somatostatin Receptor 5) • DRD2 (Dopamine Receptor D2)
|
SSTR2 expression • SSTR5 expression • SSTR Expression
|
Signifor (pasireotide)
7ms
Long Term Safety and Efficacy of Pasireotide s.c. in Patients With Cushing's Disease (clinicaltrials.gov)
P=N/A, N=151, Completed, RECORDATI GROUP | Recruiting --> Completed | Trial completion date: May 2024 --> Jul 2023
Trial completion • Trial completion date
|
Signifor (pasireotide)
7ms
Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing's disease receiving pasireotide treatment: post hoc analyses from the SOM230B2219 study. (PubMed, Front Endocrinol (Lausanne))
Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 μg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks...Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.
Retrospective data • Journal
|
SSTR (Somatostatin Receptor) • CD86 (CD86 Molecule)
|
metformin • Signifor (pasireotide) • Signifor LAR (pasireotide long acting release)
8ms
Real-World Study (RWS) of Lanreotide Autogel (LAN) for the Treatment of Patients With Acromegaly in China (clinicaltrials.gov)
P=N/A, N=129, Active, not recruiting, Ipsen | Recruiting --> Active, not recruiting | N=210 --> 129
Enrollment closed • Enrollment change • Real-world evidence • Real-world
|
IGF1 (Insulin-like growth factor 1)
|
Somatuline Depot (lanreotide prolonged-release subcutaneous)
8ms
Long-term pasireotide therapy in acromegaly: extensive real-life experience of a referral center. (PubMed, J Endocrinol Invest)
Pasireotide is effective and safe in the long-term. Hyperglycemia is a common event and is manageable even without insulin treatment.
Journal
|
SSTR (Somatostatin Receptor) • IGF1 (Insulin-like growth factor 1)
|
Signifor (pasireotide)
8ms
Changes in multi-modality management of acromegaly in a tertiary centre over 2 decades. (PubMed, Pituitary)
The vast majority of patients with acromegaly now have successful disease control with a multimodal approach. They reached biochemical control sooner in the most recent half of the study period. Future work should focus on those patients who are still uncontrolled and on the sequelae of the disease.
Journal
|
IGF1 (Insulin-like growth factor 1)
8ms
ADPKD648: Outcome of ADPKD With Octreotide LAR (clinicaltrials.gov)
P=N/A, N=70, Recruiting, Mario Negri Institute for Pharmacological Research | Not yet recruiting --> Recruiting
Enrollment open • Metastases
|
octreotide acetate
8ms
A Study of Pasireotide in People With Prolactinoma (clinicaltrials.gov)
P2, N=10, Recruiting, Memorial Sloan Kettering Cancer Center
New P2 trial
|
PRL (Prolactin)
|
Signifor (pasireotide)
9ms
IGF-2-mediated hypoglycemia: a case series and review of the medical therapies for refractory hypoglycemia. (PubMed, Endocrinol Diabetes Metab Case Rep)
Surgical resection of the associated tumour is curative in most NICTH cases. When the tumour is unresectable, moderate-dose glucocorticoids, low-dose glucocorticoids in combination with recombinant growth hormone, and pasireotide are medical therapies with promising results in controlling NICTH.
Review • Journal
|
IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2) • IGFBP3 (Insulin-like growth factor binding protein 3)
|
IGF2 elevation
|
Signifor (pasireotide)
9ms
Efficacy of pasireotide LAR for acromegaly: a prolonged real-world monocentric study. (PubMed, Front Endocrinol (Lausanne))
Tumor shrinkage was observed in 6 out of 7 evaluated responders, with no cases of size increase during the long-term follow-up. Pas-LAR is effective and safe and the early identification of responders is possible just after the first administration.
Journal • Real-world evidence • Real-world
|
IGF1 (Insulin-like growth factor 1)
|
Signifor (pasireotide) • Signifor LAR (pasireotide long acting release)
9ms
PASIREOCHIP: Pasireotide to Reduce Clinically Relevant Digestive Leakage After Complete Cytoreductive Surgery (CRS) Plus Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) for Peritoneal Carcinomatosis (clinicaltrials.gov)
P2, N=6, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=217 --> 6 | Trial completion date: Sep 2023 --> Feb 2024 | Suspended --> Terminated | Trial primary completion date: Jul 2023 --> Feb 2024; No more experimental drugs available
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Surgery
|
Signifor (pasireotide)