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streptozotocin + cisplatin + spironolactone + lomustine

Development stage
Discontinued
Lead developer
Michigan State University
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a non-standard, multi-agent investigational anticancer combination consisting of four small molecule drugs: **streptozotocin**, **cisplatin**, **spironolactone**, and **lomustine**. - **Streptozotocin** is an alkylating agent and nitrosourea antibiotic primarily used for pancreatic neuroendocrine tumors, inducing DNA damage by methylation and carbamoylation. - **Cisplatin** is a platinum-based chemotherapeutic that induces DNA crosslinks, thereby inhibiting DNA synthesis and function, primarily resulting in cell death in rapidly dividing cells. - **Spironolactone** is a mineralocorticoid (aldosterone) receptor antagonist and anti-androgen used for its diuretic and hormonal effects, with emerging evidence for potential anti-cancer properties, particularly in prostate and cancer stem cell modulation. - **Lomustine** is a nitrosourea alkylating agent used particularly for brain tumors and certain hematological malignancies, acting by causing crosslinking of DNA and RNA, thereby inhibiting replication and transcription. The precise rationale or clinical evidence for this exact four-drug combination is not available in the literature, though streptozotocin and cisplatin have been used in regimens for advanced neuroendocrine tumors and other rare malignancies, while spironolactone is being explored for its ancillary anti-tumor effects. Lomustine is generally reserved for tumors refractory to first-line alkylators. Their combination would be expected to have cumulative myelotoxic, nephrotoxic, and other serious adverse effects.

02

Targets

MR (Mineralocorticoid receptor)AR (Adrenergic receptors)DNA

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