, Volume 27, Issue 3, pp 213–224 | Cite as

Regorafenib for Gastrointestinal Malignancies

From Preclinical Data to Clinical Results of a Novel Multi-Target Inhibitor
  • Giuseppe Aprile
  • Marianna Macerelli
  • Francesco Giuliani
Review Article


Intracellular signals for cancer cell growth, proliferation, migration, and survival are frequently triggered by protein tyrosine kinases (TKs). The possibility of disrupting core disease pathways has led to development and widespread clinical use of specific TK inhibitors that in the past decade have markedly changed treatment strategies and impacted on overall outcomes. However, intrinsic resistance may limit the benefit of these drugs, and multiple escape routes compensate for the inhibited signaling. The disruption of several points of the same pathway and the simultaneous interference with different intracellular oncogenic processes have both been recognized as valuable strategies to maximize the therapeutic potential of this class of agents. In this scenario, regorafenib has emerged as a novel, orally active, multitarget compound with potent activity against a number of angiogenic and stromal TKs, including vascular endothelial growth factor receptor 2 (VEGFR-2), tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE-2), fibroblast growth factor receptor 1 (FGFR-1), and platelet-derived growth factor receptor (PDGFR). Moreover, the drug has the capability of blocking KIT, RET and V600 mutant BRAF. Starting from interesting preclinical results, this review describes the clinical development of regorafenib in gastrointestinal malignancies, focusing on data derived from cutting edge clinical trials that have provided evidence of efficacy in pretreated patients with advanced colorectal cancer or gastrointestinal stromal tumors.



The authors want to thank Dr Jessica Menis, Clinical Fellow, EORTC, Brussels, Belgium and Dr Masoud Saman, Department of Otolaryngology – Head and Neck Surgery, New York Eye and Ear Infirmary, NY, USA for their valuable comments and friendly contribution in reviewing the manuscript.

Competing interest statement

The authors declare they have no competing financial interests.

Funding source

No sponsors were involved in the writing of the manuscript or in the decision to submit the manuscript for publication.


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Giuseppe Aprile
    • 1
  • Marianna Macerelli
    • 1
  • Francesco Giuliani
    • 2
  1. 1.Department of Medical OncologyUniversity and General HospitalUdineItaly
  2. 2.Department of Medical OncologyNational Cancer Institute “G. Paolo II”BariItaly

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