Related Experiment Video

Updated: Jan 14, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Synergistic mechanisms and clinical translation of regorafenib combination therapies

Shaokui Liang1,2, Dayuan Zheng1,2, Tong Chu1,2

  • 1State Key Laboratory of Mechanism and Quality of Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 999078, China.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|January 12, 2026
PubMed

Insights

Regorafenib combinations show improved efficacy in advanced solid tumors by targeting multiple cell death pathways and oncogenic signals. Strategies to overcome resistance and improve delivery are key for future biomarker-driven treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Regorafenib, initially a monotherapy, is now integral to combination regimens for advanced solid tumors.
  • Its multi-targeted profile drives its expanded therapeutic role.

Purpose of the Study:

  • To systematically review the synergistic mechanisms of regorafenib in combination therapies.
  • To translate mechanistic insights into clinical practice and explore resistance-mitigation strategies.

Main Methods:

  • Systematic review of regorafenib's mechanisms of action.
  • Analysis of clinical data for combination regimens, including with immune checkpoint inhibitors.
  • Synthesis of strategies for overcoming resistance and optimizing drug delivery.

Main Results:

  • Regorafenib combinations induce cell death (apoptosis, autophagy, ferroptosis) and block oncogenic pathways (MAPK, PI3K/AKT, STAT3).
  • Combinations show breakthrough efficacy in microsatellite-stable colorectal cancer and hepatocellular carcinoma.
  • Strategies to overcome resistance include targeting compensatory pathways and using nanocarriers.

Conclusions:

  • Regorafenib's multi-targeted action supports its role in combination therapies for advanced solid tumors.
  • Future directions emphasize biomarker-driven selection and integrating novel agents to enhance efficacy and overcome resistance.
Keywords:
Clinical translationCombination therapyDrug resistanceRegorafenibSynergistic mechanismsTumor microenvironment

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