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Maintenance Therapy for Pancreatic Cancer, a New Approach Based on the Synergy between the Novel Agent GP-2250 (Misetionamide) and Gemcitabine.
- Source :
- Cancers; Jul2024, Vol. 16 Issue 14, p2612, 23p
- Publication Year :
- 2024
-
Abstract
- Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with rising incidences worldwide and poor survival. GP-2250 is an emerging agent showing a high antineoplastic capacity. Currently, GP-2250 is under phase I clinical trial for PDAC. This study was the first to evaluate the antineoplastic effects of GP-2250 on pancreatic adenocarcinoma in combination with Gemcitabine in a PDAC patient-derived mouse xenograft (PDX) setting. This combination showed highly synergistic effects in a primary cell culture model, as well as in a first-line and a maintenance setting using PDX. Changes in the CD133 content of treated spheroid cultures provide first indicators for this synergism. These findings demonstrate the vast potential of this highly promising combination in the maintenance therapy of PDAC patients. The novel Oxathiazinane derivative GP-2250 (Misetionamide) displays antineoplastic activity in vitro and in vivo, as previously shown in pancreatic cancer cells and in patient-derived mouse xenografts (PDX). Currently, GP 2250 is under phase I clinical trial in pancreatic ductal adenocarcinoma (PDAC). GP-2250 in combination with Gemcitabine displays a high synergistic capacity in various primary and established pancreatic cancer cell lines. Additionally, in the eight PDX models tested, the drug combination was superior in reducing tumor volume with an aggregate tumor regression (ATR) of 74% compared to Gemcitabine alone (ATR: 10%). Similarly, in a PDX maintenance setting following two weeks of treatment with nab-Paclitaxel plus Gemcitabine, the combination of GP-2250 plus Gemcitabine resulted in outstanding tumor control (ATR: 79%) compared to treatment with Gemcitabine alone (ATR: 60%). Furthermore, GP-2250 reduced the ratio of tumor-initiating CD133<superscript>+</superscript> markers on the surface of PDAC cells in spheroid cultures, indicating a possible mechanism for the synergistic effect of both substances. Considering the high tolerability of GP 2250, these results may open up a new approach to maintenance therapy with GP-2250/Gemcitabine combination following nab-Paclitaxel plus Gemcitabine as first-line treatment. [ABSTRACT FROM AUTHOR]
- Subjects :
- ADENOCARCINOMA
BIOLOGICAL models
IN vitro studies
RESEARCH funding
ANTINEOPLASTIC agents
TREATMENT effectiveness
IN vivo studies
DESCRIPTIVE statistics
CANCER patients
PANCREATIC tumors
MICE
CELL lines
DUCTAL carcinoma
GEMCITABINE
ANIMAL experimentation
MOLECULAR structure
COMPARATIVE studies
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 16
- Issue :
- 14
- Database :
- Complementary Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 178701254
- Full Text :
- https://doi.org/10.3390/cancers16142612