Pasireotide (SOM230): Development, mechanism of action and potential applications

Schmid, Herbert A.

doi:10.1016/j.mce.2007.09.006

Cited by 290Pituitary Gland Disorders and TreatmentsNeuroendocrine Tumor Research AdvancesGrowth Hormone and Insulin-like Growth Factors

Pasireotide (SOM230): Development, mechanism of action and potential applications

Schmid, Herbert A.·2008·Molecular and Cellular Endocrinology

DOI 10.1016/j.mce.2007.09.006

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Abstract

Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue with high binding affinity for somatostatin receptor subtypes sst(1,2,3) and sst(5). Pasireotide potently suppresses GH, IGF-I and ACTH secretion, indicating potential efficacy in acromegaly and Cushing's disease. The prolonged inhibition of hormone secretion by pasireotide in animal models and expression of multiple sst receptors in carcinoid tumors suggests that pasireotide may have clinical advantages over octreotide in patients with carcinoid tumors. Direct and indirect antitumor activity has been observed in vitro with pasireotide, including sst receptor-mediated apoptosis and antiangiogenesis, suggesting a possible role for pasireotide in antineoplastic therapy. In summary, preclinical evidence, as well as preliminary results from clinical studies suggests that pasireotide is a promising new treatment for patients with symptoms of metastatic carcinoid tumors refractory or resistant to octreotide, de novo or persistent acromegaly, and that pasireotide has the potential to be the first directed medical therapy for Cushing's disease.

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The affinity of pasireotide for sst5 is higher than that of octreotide.
“The affinity of pasireotide for sst5 is higher than that of octreotide (98,99).”
From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [99]
Pasireotide is a multireceptor-targeted somatostatin analogue with high affinity for 4 of the 5 somatostatin receptor subtypes, including sst2 and sst5.
“Pasireotide is a multireceptor-targeted somatostatin analogue with high affinity for 4 of the 5 somatostatin receptor subtypes, including sst2 and sst5.”
From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [99]

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Medical Therapy of Acromegaly
Feelders, R., Hofland, L., van Aken, M. V., Neggers, S., Lamberts, S., de Herder, W. D., & van der Lely, A. J. (2009) · Drugs · doi:10.2165/11318510-000000000-00000 · Cited by 51 · see citing works
“[94] Pasireotide has a 40-fold higher binding affinity for the sst5 receptor and could thus be a potent GH inhibitor, particularly in octreotide-resistant adenomas.”
Background
Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis
Imhof, A., Glück, L., Gajda, M., Lupp, A., Bräuer, R., Schaible, H., & Schulz, S. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30410 · Cited by 52 · see citing works
“The expression of SSTR1, SSTR2A, SSTR3, and SSTR5 in dorsal root ganglia was examined by immunohistochemistry.”
BackgroundInfluential
AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients
Daly, A., Rostomyan, L., Betea, D., Bonneville, J., Villa, C., Pellegata, N., Waser, B., Reubi, J., Stephan, C. W., Christ, E., et al. (2019) · Endocrine Connections · doi:10.1530/ec-19-0004 · Cited by 50
Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures.
Mohamed, A., Blanchard, M.-P., Albertelli, M., Barbieri, F., Brue, T., Niccoli, P., Delpero, J., Monges, G., Garcia, S., Ferone, D., et al. (2014) · Endocrine-Related Cancer · doi:10.1530/erc-14-0086 · Cited by 50
“5-fold lower affinity for sst2 (Schmid 2008).”
Pasireotide in the Personalized Treatment of Acromegaly
Puig-Domingo, M., Bernabéu, I., Picó, A., Biagetti, B., Gil, J., Álvarez-Escolá, C., Jordà, M., Marqués-Pamies, M., Soldevila, B., Gálvez, M., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.648411 · Cited by 49
The Expanding Role of Somatostatin Analogs in Gastroenteropancreatic and Lung Neuroendocrine Tumors
Cives, M., & Strosberg, J. (2015) · Drugs · doi:10.1007/s40265-015-0397-7 · Cited by 49 · see citing works
“The ERK1/2/ PI3K/AKT signaling is also down-regulated after simultaneous stimulation of SSTR1, SSTR2, and SSTR5 through the sequential activation of Janus kinase 2 (JAK2)/src tyrosine kinases and Src homology phosphatase-2 (SHP-2) [50].”
BackgroundInfluential
Somatostatin and somatostatin receptors: from basic concepts to clinical applications.
Martino, M. D. D., Hofland, L., & Lamberts, S. (2010) · Progress in Brain Research · doi:10.1016/s0079-6123(10)82011-4 · Cited by 49 · see citing works
Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma.
Coopmans, E. C., van Meyel, S. V., Pieterman, K., van Ipenburg, J. V., Hofland, L., Donga, E., Daly, A., Beckers, A., van der Lely, A. J., & Neggers, S. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0279 · Cited by 47 · see citing works
Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study
Petersenn, S., Farrall, A., Block, C., Melmed, S., Schopohl, J., Caron, P., Cuneo, R., Kleinberg, D., Colao, A., Ruffin, M., et al. (2013) · Pituitary · doi:10.1007/s11102-013-0478-0 · Cited by 47
“However, pituitary tumors in patients with acromegaly express both sst2 and sst5 [10].”
Background
How to Position Pasireotide LAR Treatment in Acromegaly
Coopmans, E. C., Muhammad, A., van der Lely, A. J., Janssen, J., & Neggers, S. (2019) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2018-01979 · Cited by 46
GEP-NETs update: Biotherapy for neuroendocrine tumours.
Alonso-Gordoa, T., Capdevila, J., & Grande, E. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0354 · Cited by 45
Somatostatin analogs for the treatment of neuroendocrine tumors
Culler, M., Öberg, K., Arnold, R., Krenning, E., Sevilla, I., & Díaz, J. (2011) · Cancer Metastasis Review · doi:10.1007/s10555-011-9293-0 · Cited by 45
“The new multireceptor somatostatin analog pasireotide (SOM230) described above, as well as chimeric molecules, such as BIM-23A760 (a single compound with both somatostatinergic and dopaminergic activity), may also become part of the clinical management of GEP-NETs.”
BackgroundInfluential
Pharmacological management of acromegaly: a current perspective.
Manjila, S., Wu, O. C., Khan, F. R., Khan, M. M., Arafah, B., & Selman, W. (2010) · Neurosurgical Focus · doi:10.3171/2010.7.focus10168 · Cited by 45
Risk factors and management of pasireotide-associated hyperglycemia in acromegaly
Gadelha, M., Gu, F., Bronstein, M., Brue, T., Fleseriu, M., Shimon, I., van der Lely, A. J., Ravichandran, S., Kandra, A., Pedroncelli, A., et al. (2020) · Endocrine Connections · doi:10.1530/ec-20-0361 · Cited by 44
“Pasireotide binds with high affinity to four of the five somatostatin receptor subtypes (SST): SST 1 , SST 2 , SST 3 and SST 5 (14), with highest affinity for SST 5 (39-fold higher affinity than octreotide) (15).”
Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors
Pokuri, V., Fong, M., & Iyer, R. (2016) · Current Oncology Reports · doi:10.1007/s11912-015-0492-7 · Cited by 44 · see citing works
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study
Wolin, E., Hu, K., Hughes, G., Bouillaud, E., Giannone, V., & Reséndiz, K. H. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2202-1 · Cited by 44
“Pasireotide (SOM230) is a novel, multireceptor ligand SSA that binds with high affinity to four of the five somatostatin receptor subtypes (sst1–3,5) [12].”
Background
Effects of Bone Morphogenetic Protein (BMP) on Adrenocorticotropin Production by Pituitary Corticotrope Cells: Involvement of Up-Regulation of BMP Receptor Signaling by Somatostatin Analogs
Tsukamoto, N., Otsuka, F., Miyoshi, T., Yamanaka, R., Inagaki, K., Yamashita, M., Otani, H., Takeda, M., Suzuki, J., Ogura, T., et al. (2010) · Endocrinology · doi:10.1210/en.2009-1102 · Cited by 44 · see citing works
“For instance, octreotide is a SSTR-2-prefering agonist, and pasireotide (also called SOM230) is a multireceptor agonist that binds to SSTR-1, -2, -3, and -5 with high affinity, having a 30- and 40-fold higher and prolonged affinity to SSTR-1 and SSTR-5, respectively, as compared with the effects of octreotide (3, 4).”
Background
Treatment of unresectable skull base meningiomas with somatostatin analogs.
Schulz, C., Mathieu, R., Kunz, U., & Mauer, U. (2011) · Neurosurgical Focus · doi:10.3171/2011.1.focus111 · Cited by 41
Somatostatin receptors in non-neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors.
Hasskarl, J., Kaufmann, M., & Schmid, H. (2011) · Future Oncology · doi:10.2217/fon.11.66 · Cited by 40
Self-citation
T2-signal intensity, SSTR expression, and somatostatin analogs efficacy predict response to pasireotide in acromegaly.
Coopmans, E. C., Schneiders, J., El-Sayed, N., Erler, N., Hofland, L., van der Lely, A. J., Pétrossians, P., Potorac, J., Muhammad, A., & Neggers, S. (2020) · European Journal of Endocrinology · doi:10.1530/eje-19-0840 · Cited by 38
Pasireotide protects mammalian cochlear hair cells from gentamicin ototoxicity by activating the PI3K–Akt pathway
Kucharava, K., Sekulic-Jablanovic, M., Horvath, L., Bodmer, D., & Petkovic, V. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1386-7 · Cited by 38
Biological targeted therapies in patients with advanced enteropancreatic neuroendocrine carcinomas.
Fazio, N., Cinieri, S., Lorizzo, K., Squadroni, M., Orlando, L., Spada, F., Maiello, E., Bodei, L., Paganelli, G., Fave, G. D., et al. (2010) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(10)70026-8 · Cited by 38
Anti-metastatic potential of somatostatin analog SOM230: Indirect pharmacological targeting of pancreatic cancer-associated fibroblasts
Moatassim-Billah, S., Duluc, C., Samain, R., Jean, C., Perraud, A., Decaup, E., Cassant‐Sourdy, S., Bakri, Y., Sèlves, J., SCHMID, H. A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9296 · Cited by 45 · see citing works
“Pasireotide (SOM230) is a new, more stable analog with a plasma half-life of 12 hours [12].”
BackgroundSelf-citation
Somatostatin, somatostatin analogs and somatostatin receptor dynamics in the biology of cancer progression.
Ruscica, M., Arvigo, M., Steffani, L., Ferone, D., & Magni, P. (2013) · Current molecular medicine · doi:10.2174/1566524011313040008 · Cited by 37 · see citing works
“, SOM230, KE108 and BIM-23A779) to be potentially effective not only in patients with acromegaly or carcinoid tumors who respond to octreotide, but also in patients unresponsive or refractory to octreotide, as well as in other diseases associated with ssts expression other than sst2, then increasing tumor responsivene…”
BackgroundInfluential
Translation of Molecular Pathways into Clinical Trials of Neuroendocrine Tumors
Pavel, M. E. (2012) · Neuroendocrinology · doi:10.1159/000336089 · Cited by 34 · see citing works
Pasireotide (SOM230), a Novel Multireceptor‐Targeted Somatostatin Analogue, Is Well Tolerated When Administered as a Continuous 7‐Day Subcutaneous Infusion in Healthy Male Volunteers
Petersenn, S., Unger, N., Hu, K., Weisshaar, B., Zhang, Y., Bouillaud, E., Reséndiz, K. H., Wang, Y.-F., & Mann, K. (2012) · Journal of clinical pharmacology · doi:10.1177/0091270011408727 · Cited by 36 · see citing works
Safety review: Dose optimization of somatostatin analogs in patients with acromegaly and neuroendocrine tumors
Ludlam, W., & Anthony, L. (2011) · Advances in Therapy · doi:10.1007/s12325-011-0062-9 · Cited by 35
Effect of SOM230 (Pasireotide) on Corticotropic Cells: Action in Dogs with Cushing’s Disease
Castillo, V., Theodoropoulou, M., Stalla, J., Gallelli, M., Cabrera-Blatter, M. F., Haedo, M., Labeur, M., Schmid, H., Stalla, G., & Arzt, E. (2011) · Neuroendocrinology · doi:10.1159/000327429 · Cited by 35
Self-citation
A pilot study of the effects of the somatostatin analog pasireotide in postoperative dumping syndrome
Deloose, E., Bisschops, R., Holvoet, L., Arts, J., De Wulf, D., Caenepeel, P., Lannoo, M., Vanuytsel, T., Andrews, C., & Tack, J. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12333 · Cited by 35 · see citing works
Investigational drugs targeting somatostatin receptors for treatment of acromegaly and neuroendocrine tumors
Giustina, A., Mazziotti, G., Maffezzoni, F., Amoroso, V., & Berruti, A. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.942728 · Cited by 34 · see citing works
“Pasireotide shows a lower degree in SSTR2 internalization and induces fast recycling to the plasma membrane, counteracting desensitization and resulting in a longer-lasting response [149,150].”
Background
Management of acromegaly in Latin America: expert panel recommendations
Barkan, A., Bronstein, M., Bruno, O., Cob, A., Espinosa-de-los-Monteros, A., Gadelha, M., Garavito, G., Guitelman, M., Mangupli, R., Mercado, M., et al. (2009) · Pituitary · doi:10.1007/s11102-009-0206-y · Cited by 34
“Finally, other medical options for somatostatin analogue-resistant acromegaly may become available in the near future, including agents with multiple sst activity (such as pasireotide [SOM230] which has high affinity for sst1,2,3 and sst5) [61], agents with selective affinity for sst2 and sst5 (such as BIM-23244) [62]…”
Background
Somatostatin analogues: treatment of pituitary and neuroendocrine tumors.
Colao, A., Faggiano, A., & Pivonello, R. (2010) · Progress in Brain Research · doi:10.1016/s0079-6123(10)82012-6 · Cited by 34 · see citing works
Safety, tolerability, and pharmacokinetics of a single dose of pasireotide long-acting release in healthy volunteers: a single-center Phase I study.
Dietrich, H., Hu, K., Ruffin, M., Song, D., Bouillaud, E., Wang, Y.-F., & Hasskarl, J. (2012) · European Journal of Endocrinology · doi:10.1530/eje-11-0773 · Cited by 33 · see citing works
An Open-Label Dose-Escalation Study of Once-Daily and Twice-Daily Pasireotide in Healthy Volunteers: Safety, Tolerability, and Effects on Glucose, Insulin, and Glucagon Levels
Shenouda, M., Maldonado, M., Wang, Y.-F., Bouillaud, E., Hudson, M., Nesheiwat, D., & Hu, K. (2014) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e31824c3eb4 · Cited by 31 · see citing works
Somatostatin receptor biology in neuroendocrine and pituitary tumours: part 2 – clinical implications
Cakir, M., Dworakowska, D., & Grossman, A. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01125_1.x · Cited by 31
“As it potently suppresses GH and IGF-I secretion and, furthermore multiple SSTR expression is a feature of carcinoid tumours, pasireotide may have potential efficacy in acromegaly and the carcinoid syndrome as well [36].”
Background
Somatostatin and somatostatin receptors: implications for neoplastic growth and cancer biology
Msaouel, P., Galanis, E., & Koutsilieris, M. (2009) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780903176399 · Cited by 31 · see citing works
“Currently, the furthest developed multi-receptor SM-A is pasireotide (SOM230) which binds to sst1, sst2, sst3 and sst5 with high affinity while exhibiting minimal affinity for sst4 [82-84].”
Background
Somatostatin stimulates menin gene expression by inhibiting protein kinase A.
Mensah-Osman, E., Zavros, Y., & Merchant, J. (2008) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00607.2007 · Cited by 31
“Therefore, somatostatin receptor regulation of menin will likely contribute to our mechanistic understanding of why somatostatin analogs are effective treatments for a variety of endocrine tumors (14, 47, 51).”
Background
Expression and functional analysis of dopamine receptor subtype 2 and somatostatin receptor subtypes in canine cushing's disease.
de Bruin, C., Hanson, J., Meij, B. P., Kooistra, H., Waaijers, A., Uitterlinden, P., Lamberts, S., & Hofland, L. (2008) · Endocrinology · doi:10.1210/en.2008-0244 · Cited by 31 · see citing works
“explain the low sst2 expression in human corticotroph adenomas (5, 46, 47).”
Background
FDA's stamp of approval: Unveiling peptide breakthroughs in cardiovascular diseases, ACE, HIV, CNS, and beyond
Musaimi, O. A. (2024) · Journal of Peptide Science · doi:10.1002/psc.3627 · Cited by 31 · see citing works
Recent advances in peptide-based therapeutic strategies for breast cancer treatment
Li, L., Duns, G. J., Dessie, W., Cao, Z., Ji, X., & Luo, X. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1052301 · Cited by 31 · see citing works
Phase I Study of Pasireotide (SOM 230) and Everolimus (RAD001) in Advanced Neuroendocrine Tumors
Chan, J., Ryan, D., Zhu, A., Abrams, T., Wolpin, B., Malinowski, P., Regan, E., Fuchs, C., & Kulke, M. (2012) · Endocrine-Related Cancer · doi:10.1530/erc-11-0382 · Cited by 30 · see citing works
“Pasireotide (SOM230) is a multi-ligand somatostatin analog that has high binding affinity to the somatostatin receptors sst1, sst2, sst3, and sst5 (Schmid 2008).”
Background
Somatostatin analogues do not prevent carcinoid crisis.
Guo, L., & Tang, C.-W. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.16.6679 · Cited by 30 · see citing works
“(Schmid, 2008) Pasireotide may”
Background
Safety and efficacy of pasireotide in dumping syndrome—results from a phase 2, multicentre study
Tack, J. F., Aberle, J., Arts, J., Laville, M., Oppert, J., Bender, G., Bhoyrul, S., McLaughlin, T., Yoshikawa, T., Vella, A., et al. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14664 · Cited by 35 · see citing works
“4-fold lower affinity for SSTR2.(22,23) SSTR2 and SSTR5 also play important roles in blood glucose regulation by inhibiting the secretion of glucagon (SSTR2) and insulin (SSTR2 and SSTR5).”
BackgroundInfluential

Authors: Schmid, H. A.
Affiliations: Novartis (Switzerland) (CH)
Corresponding author: Schmid, Herbert A.
Venue: Molecular and Cellular Endocrinology
Publisher: Elsevier BV
Published: 2008-05
Volume: 286
Issue: 1-2
Pages: 69-74
ISSN: 0303-7207 (ISSN-L)
DOI: 10.1016/j.mce.2007.09.006
OpenAlex: W2012451298
Cited by: 290
References: 0
Citations by year: 2026: 3 · 2025: 5 · 2024: 13 · 2023: 10 · 2022: 9 · 2021: 11 · 2020: 11 · 2019: 12 · 2018: 18 · 2017: 15 · 2016: 19 · 2015: 17 · 2014: 23 · 2013: 21 · 2012: 30
FWCI: 2.34
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular and Cellular Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords: pasireotide, somatostatin analogues, somatostatin receptor subtypes, acromegaly, Cushing's disease, carcinoid tumor, octreotide, anticancer activity, apoptosis, angiogenesis inhibition, growth hormone suppression, ACTH suppression
MeSH terms: Acromegaly, Adrenocorticotropic Hormone, Animals, Carcinoid Tumor, Humans, Insulin-Like Growth Factor I, Somatostatin, Growth Hormone, Structure-Activity Relationship, Octreotide, Receptors, Somatostatin, Antineoplastic Agents, Hormonal, Drug Resistance, Neoplasm, Pituitary ACTH Hypersecretion

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Pasireotide (SOM230): Development, mechanism of action and potential applications

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