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Ravegnini et al. Cancer Drug Resist 2019;2:107-15 Cancer
DOI: 10.20517/cdr.2019.02 Drug Resistance

Review Open Access

Somatic pharmacogenomics of gastrointestinal
stromal tumor

Gloria Ravegnini, Patrizia Hrelia , Sabrina Angelini #
#
Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy.
# These authors equally contributed to this work.
Correspondence to: Prof. Sabrina Angelini, Department of Pharmacy and Biotechnology, University of Bologna, Bologna
40126, Italy. E-mail: s.angelini@unibo.it

How to cite this article: Ravegnini G, Hrelia P, Angelini S. Somatic pharmacogenomics of gastrointestinal stromal tumor. Cancer
Drug Resist 2019;2:107-15. http://dx.doi.org/10.20517/cdr.2019.02

Received: 7 Dec 2018 First Decision: 21 Dec 2018 Revised: 24 Jan 2019 Accepted: 11 Feb 2019 Published: 19 Mar 2019
Science Editor: Enrico Mini Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Gastrointestinal stromal tumors (GISTs) are rare entities, which, however, represent the most common mesenchymal
tumor of the gastrointestinal tract. The discovery of gain of function mutations on KIT and PDGFRA receptor genes led to
a deep revolution in the knowledge of this tumor. This paved the way to the introduction of imatinib and other tyrosine-
kinase inhibitors (TKIs), which terrifically revolutionized the prognosis of GIST patients. Currently, it is well established
that tumor mutational status is the main player in clinical outcome; however, with the research advances, it has been
slowly understood that GIST landscape is more complex than expected and the TKIs available are not effective for all
the GIST subtypes. For this reason, in the era of tailored/personalized medicine, each GIST patient should be considered
individually and genetic consult should be the first step to take in consideration in the therapeutic decision making
process.

Keywords: Gastrointestinal stromal tumor, imatinib, pharmacogenomics, pharmacogenetics, tyrosine-kinase inhibitors

INTRODUCTION
Gastrointestinal stromal tumors (GISTs) are rare entities, which, however, represent the most common
[1,2]
mesenchymal tumor of the gastrointestinal system . Before the groundbreaking identification of activating
[3]
mutations in the KIT tyrosine kinase receptor (TKR) gene in 1998 , GISTs were considered as a devastating
disease due to scarce response to chemotherapy and radiotherapy. Luckily, the discovery of gain-of-function
mutations on KIT and PDGFRA receptor genes led to a deep revolution in the knowledge of this tumor and

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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