TY - JOUR
T1 - Mechanisms of antineoplastic action of somatostatin analogs
AU - Pollak, Michael N.
AU - Schally, Andrew V.
N1 - Funding Information:
To whom requests for reprints should be addressed at 3755 Cote St. Catherine Road, Montreal, Quebec, Canada H3T 1E2. E-mail: MD49@MUSICA.MCGILL.CA. Dr. Pollak's laboratory research is funded by the National Cancer Institute of Canada and he is supported by the Fonds de la Recherche en Sante du Quebec and the Reisman Family Foundation as a Clinician Scientist at The Lady Davis Research Institute of McGill University. Dr. A. V. Schally is supported by the Medical Research Service of the Veteran Affairs Department.
PY - 1998/2
Y1 - 1998/2
N2 - Over the past decade, impressive antineoplastic activity of somatostatin analogs has been demonstrated in many tumor models. More recent research has provided information regarding mechanisms underlying the antiproliferative and apoptosis-inducing actions of these compounds. These include both 'direct' mechanisms that are sequellae of binding of somatostatin analogs to somatostatin receptors present on neoplastic cells and 'Indirect' mechanisms related to effects of somatostatin analogs on the host. The upregulation of intracellular tyrosine phosphatase activity triggered by binding of ligands to the type II somatostatin receptor has received considerable attention as a direct mechanism, not only because this activity is the converse of the tyrosine kinase activity associated with many peptide mitogen receptors, but also because the type II somatostatin receptor is frequently expressed by common human neoplasms, including breast cancer. The potential importance of indirect mechanisms of action of somatostatin analogs, such as alterations in host insulin-like growth factor physiology, is emphasized by the in vivo antineoplastic activity of these compounds against somatostatin receptor- negative neoplasms. Clinical efficacy and a favorable toxicity profile of somatostatin analogs in the treatment of relatively uncommon conditions such as acromegaly end neuroendocrine tumors have already been demonstrated. Preclinical data now are sufficient to justify controlled clinical trials in breast, prostate, and pancreatic cancer. The development of monthly depot formulations will facilitate the clinical evaluation of somatostatin analogs for these and other indications.
AB - Over the past decade, impressive antineoplastic activity of somatostatin analogs has been demonstrated in many tumor models. More recent research has provided information regarding mechanisms underlying the antiproliferative and apoptosis-inducing actions of these compounds. These include both 'direct' mechanisms that are sequellae of binding of somatostatin analogs to somatostatin receptors present on neoplastic cells and 'Indirect' mechanisms related to effects of somatostatin analogs on the host. The upregulation of intracellular tyrosine phosphatase activity triggered by binding of ligands to the type II somatostatin receptor has received considerable attention as a direct mechanism, not only because this activity is the converse of the tyrosine kinase activity associated with many peptide mitogen receptors, but also because the type II somatostatin receptor is frequently expressed by common human neoplasms, including breast cancer. The potential importance of indirect mechanisms of action of somatostatin analogs, such as alterations in host insulin-like growth factor physiology, is emphasized by the in vivo antineoplastic activity of these compounds against somatostatin receptor- negative neoplasms. Clinical efficacy and a favorable toxicity profile of somatostatin analogs in the treatment of relatively uncommon conditions such as acromegaly end neuroendocrine tumors have already been demonstrated. Preclinical data now are sufficient to justify controlled clinical trials in breast, prostate, and pancreatic cancer. The development of monthly depot formulations will facilitate the clinical evaluation of somatostatin analogs for these and other indications.
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U2 - 10.3181/00379727-217-44216
DO - 10.3181/00379727-217-44216
M3 - Short survey
C2 - 9452137
AN - SCOPUS:0031941299
VL - 217
SP - 143
EP - 152
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
SN - 0037-9727
IS - 2
ER -