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<p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases with few treatment options. The aberrant activation of SRC PDAC suggests it as a promising therapeutic target. Here, we evaluated the antitumor activity of olverembatinib, a novel multi-target tyrosine kinase inhibitor, as a single agent and in combination with gemcitabine, the standard chemotherapeutic backbone for PDAC treatment. Our results demonstrated that olverembatinib showed a potent anti-tumor effect and significantly enhanced the sensitivity of PDAC to gemcitabine both in vitro and in vivo. Mechanistically, olverembatinib inhibited the SRC/AKT/cMYC signaling pathway, leading to cell cycle arrest, suppression of metastasis, and induction of apoptosis. For combination with gemcitabine, the JAK1-STAT1 might serve as an important mechanistic basis of synergy. Clinically, olverembatinib exhibited promising efficacy in patients with advanced PDAC who had failed multiple prior lines of therapies, including gemcitabine-based treatment. These findings suggest that olverembatinib, either as monotherapy or in combination with gemcitabine, represents a promising novel therapeutic strategy for the treatment of PDAC.</p>

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Olverembatinib, a novel BCR-ABL tyrosine kinase inhibitor, exhibits anti-tumor activity and synergizes with gemcitabine in pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Zengfei Xia,
  • Runduan Lin,
  • Fan Luo,
  • Qiuyun Luo,
  • Jing Yang,
  • Shan Shi,
  • Yan Li,
  • Jiaxing Cao,
  • Miaozhen Qiu,
  • Lin Zhang,
  • Wenlong Guan,
  • Dajun Yang

摘要

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases with few treatment options. The aberrant activation of SRC PDAC suggests it as a promising therapeutic target. Here, we evaluated the antitumor activity of olverembatinib, a novel multi-target tyrosine kinase inhibitor, as a single agent and in combination with gemcitabine, the standard chemotherapeutic backbone for PDAC treatment. Our results demonstrated that olverembatinib showed a potent anti-tumor effect and significantly enhanced the sensitivity of PDAC to gemcitabine both in vitro and in vivo. Mechanistically, olverembatinib inhibited the SRC/AKT/cMYC signaling pathway, leading to cell cycle arrest, suppression of metastasis, and induction of apoptosis. For combination with gemcitabine, the JAK1-STAT1 might serve as an important mechanistic basis of synergy. Clinically, olverembatinib exhibited promising efficacy in patients with advanced PDAC who had failed multiple prior lines of therapies, including gemcitabine-based treatment. These findings suggest that olverembatinib, either as monotherapy or in combination with gemcitabine, represents a promising novel therapeutic strategy for the treatment of PDAC.