Streptozotocin, 1982–2022: Forty Years from the FDA’s Approval to Treat Pancreatic Neuroendocrine Tumors

Abstract

On May 1982, the US Food and Drug Administration (FDA) approved the use of streptozotocin to treat pancreatic neuroendocrine tumors (panNETs). Thus, this year marks forty years since that landmark date. This review of streptozotocin to treat panNETs is intended to commemorate this anniversary. A historical perspective of chemical structure, pharmacokinetics, and mechanism of action of streptozotocin is followed by data from prospective and retrospective clinical studies. The last section of the review addresses the latest aspects and takes note of the prospects that lie ahead on the future horizon of the use of streptozotocin to treat panNETs, including ongoing clinical trials.

DNA Adducts in Cancer Chemotherapy

“…It is a glucosamine-derived nitrosourea, found to have diabetogenic activity shortly after its first discovery from a soil microorganism in 1963 . Streptozotocin can be selectively transported into pancreatic β-cells by the highly expressed glucose transporter 2 protein (GLUT2) …”

Chemoembolization Beyond Hepatocellular Carcinoma: What Tumors Can We Treat and When?

“…Some groups have reported good outcomes with streptozotocin as well, noting streptozotocin-TACE requires treatment under general anesthesia due to pain associated with its administration, limiting its use. [108][109][110] Given the goals of treatment for NETs are different from other cancers and include control of hormonal symptoms and disease control (rather than cure), results in this population are typically described in multiple ways. In addition to typical survival data (OS, PFS, etc.…”

Streptozotocin as a tool for induction of rat models of diabetes: a practical guide

“…Streptozotocin (also called Streptozocin) or 2-deoxy-2(([methyl(nitroso)amino]carbonyl)amino)-(α and β)-D-glucopyranose (Thurston and Pysz, 2021[ 134 ]), was discovered in 1959 as a natural antibiotic produced by Streptomyces achromogenes ; its toxicity towards pancreatic β-cells (diabetogenic action) was reported in 1963 (Capdevila et al, 2022[ 12 ]) by Rakieten (Lenzen, 2008[ 74 ]). STZ molecule (molecular formula=C8H15N3O7, molecular weight≈265 (Junod et al, 1967[ 58 ])) has two parts: (1) glucopyranosyl group, which facilitates its uptake by pancreatic β-cells by glucose transporter 2 (GLUT2) and (2) nitrosourea group, which destructs pancreatic β-cells (Capdevila et al, 2022[ 12 ]).…”

“…However, an acidic solution can cause red blood cell hemolysis in rats and provide pain and discomfort to the animal (Lee et al, 1993[ 73 ]). STZ has been used for treating pancreatic neuroendocrine tumors since 1982 after the approval of the FDA (US Food and Drug Administration) (Capdevila et al, 2022[ 12 ]). In addition to 1 g of STZ, each vial of STZ powder contains 200-220 mg citric acid (Akbarzadeh et al, 2007[ 1 ]; El-Rashedy et al, 2013[ 21 ]; Frost et al, 2015[ 28 ]), providing a pH of 3.5-4.5 after dissolving in 9.5 mL of cold 0.9 % NaCl (Akbarzadeh et al, 2007[ 1 ]; Frost et al, 2015[ 28 ]).…”