TAS-102 has a tumoricidal activity in multiple myeloma

Area of Science:

• Oncology
• Pharmacology

Background:

• Trifluridine/tipiracil (TAS-102) is approved for advanced colorectal cancer.
• Its efficacy in hematological malignancies, like multiple myeloma, remains unexplored.

Purpose of the Study:

• To investigate the therapeutic potential of TAS-102 in multiple myeloma.
• To evaluate TAS-102's efficacy both in vitro and in vivo.

Main Methods:

• Assessed TAS-102's effect on human myeloma cell lines and drug-resistant cells.
• Utilized dot blotting and immunofluorescent staining to track trifluridine incorporation.
• Conducted in vivo studies using human myeloma xenograft models.
• Evaluated combination therapy with bortezomib.

Main Results:

• TAS-102 inhibited myeloma cell proliferation (IC50: 0.64–9.10 μM) and induced apoptosis via G1 cell cycle arrest.
• Trifluridine was incorporated into myeloma cell genomic DNA, activating cGAS-STING signaling.
• TAS-102 reduced tumor progression and prolonged survival in xenograft models.
• Demonstrated efficacy against drug-resistant myeloma cells and synergistic activity with bortezomib.

Conclusions:

• TAS-102 exhibits significant anti-myeloma activity in preclinical models.
• TAS-102 is a potential novel therapeutic agent for multiple myeloma, including drug-resistant cases.