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Lonsurf + gemcitabine + nab-paclitaxel

Development stage: Unknown
Lead developer: Taiho Oncology
Modality: Nanoparticles → Drug Delivery Systems, Small Molecules
Administration: Oral, Intravenous

Overview

Lonsurf + gemcitabine + nab-paclitaxel is an experimental combination chemotherapy regimen being evaluated for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC). The regimen consists of Lonsurf—a fixed-dose oral combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil—administered alongside intravenous gemcitabine and nab-paclitaxel (albumin-bound paclitaxel). Trifluridine exerts its cytotoxic effect by incorporating into viral and cellular DNA, while tipiracil increases trifluridine bioavailability by inhibiting its degradation by thymidine phosphorylase. Gemcitabine further inhibits DNA synthesis by targeting ribonucleoside reductase and incorporating into DNA, and nab-paclitaxel arrests the cell cycle by stabilizing microtubules. This triplet combination is currently being investigated in a Phase I dose-escalation trial sponsored by Patrick Joseph Loehrer Sr. at Indiana University to determine the recommended phase 2 dose (RP2D) for patients with advanced PDAC.

Brand names: LonsurfGemzarAbraxane
Other names: trifluridine + tipiracil + gemcitabine + nab-paclitaxelTAS-102 + gemcitabine + nab-paclitaxel

Targets

CDA (Cytidine deaminase)RNR (Ribonucleotide reductase)DNA polymerase familyTYMP (Thymidine phosphorylase)TUBB (Tubulin (alpha and beta subunits))

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