Is Selinisol (Silvio) a targeted drug or a chemotherapy drug and analysis of its mechanism of action

Selinexor (trade name Xpovio) is a new type of oral selective inhibitor of nuclear export (SINE). It is not a traditional chemotherapy drug, but a new type of anti-tumor drug with a targeted mechanism of action. Its target is nuclear export protein XPO1 (Exportin-1), so it is included in the category of "targeted therapy drugs" in a broad classification. However, unlike common tyrosine kinase inhibitors (TKI) or monoclonal antibody-based targeted drugs, seliniso is a nuclear transport pathway-targeting drug with a more unique mechanism.

In normal cells, XPO1 is responsible for transporting a variety of key tumor suppressor proteins (such as p53, Rb, FOXO, etc.) from the nucleus to the cytoplasm. However, in a variety of cancer cells, overexpression of XPO1 will cause these tumor suppressor proteins to be exported to the cytoplasm too quickly, thereby losing their function of inhibiting tumor growth. By binding to XPO1, selinesol blocks its nuclear export function, allowing the tumor suppressor protein to remain in the nucleus and resume its function, thereby inducing apoptosis and growth inhibition of cancer cells.

Unlike traditional chemotherapy drugs, selinesol does not kill cells by directly damagingDNA or interfering with cell division. Instead, it achieves its anti-cancer effect by restoring the body's endogenous anti-tumor mechanism. This mechanism is highly selective and therefore causes relatively little damage to normal cells. However, because its effects affect multiple cell signaling pathways, patients may still experience side effects such as fatigue, nausea, and cytopenias during treatment, but the overall tolerability is better than most traditional chemotherapy regimens.

Selinesol has been approved by theFDA for the treatment of refractory and relapsed hematological malignancies such as multiple myeloma and diffuse largeB cell lymphoma, especially for patients who have failed multiple lines of treatment. Its unique mechanism of action provides a new way to overcome partial drug resistance and lays the foundation for future application in the field of solid tumors. Currently, multiple clinical trials are exploring its combination with other targeted drugs, immunotherapy or chemotherapy drugs in order to improve the efficacy and expand the scope of indications.

Reference materials:https://www.drugs.com/