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Updated: Apr 30, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Regorafenib inhibits colorectal tumor growth through PUMA-mediated apoptosis

Dongshi Chen1, Liang Wei2, Jian Yu2

  • 1Authors' Affiliations: University of Pittsburgh Cancer Institute; Departments of Pharmacology and Chemical Biology and.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 26, 2014
PubMed
Abstract

Insights

Regorafenib induces PUMA, a key protein, to suppress colorectal cancer growth and enhance chemotherapy effectiveness. PUMA is essential for regorafenib

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Regorafenib is approved for metastatic colorectal cancer (mCRC).
  • The precise mechanisms of regorafenib's action in mCRC cells remain unclear.
  • Understanding these mechanisms is crucial for optimizing cancer treatment strategies.

Purpose of the Study:

  • To investigate how regorafenib suppresses colorectal cancer cell growth.
  • To determine if regorafenib potentiates the effects of other chemotherapeutic drugs.
  • To elucidate the role of PUMA in mediating regorafenib's effects.

Main Methods:

  • Assessed PUMA induction by regorafenib in colorectal cancer cells.
  • Investigated PUMA's necessity for regorafenib's cytotoxic and chemosensitizing effects.
  • Utilized xenograft models to evaluate PUMA's role in vivo.

Main Results:

  • Regorafenib induces PUMA expression via the NF-κB pathway, irrespective of p53 status.
  • PUMA upregulation correlates with apoptosis and is essential for regorafenib-induced cell death.
  • PUMA deficiency abrogates regorafenib's antitumor, antiangiogenic, and chemosensitization effects in vivo.

Conclusions:

  • PUMA plays a critical role in mediating regorafenib's anticancer effects in colorectal cancer.
  • PUMA induction serves as a potential biomarker for regorafenib sensitivity.
  • Targeting the apoptotic machinery via PUMA modulation offers a strategy to enhance regorafenib efficacy.

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