Pharmacogenomics of targeted agents for personalization of colorectal cancer treatment

Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli

Research output: Contribution to journalReview article

Abstract

The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 (human epidermal growth factor receptor-2 and -3), and BRAF. A major issue with targeted treatment is early identification of patients with primary or secondary drug resistance. Pharmacogenomic research has demonstrated its value in this field, highlighting some tumor mutations that could discriminate responders from non-responders. The tumor genetic profile of the RAS/RAF pathway is needed before treatment with anti-EGFR agents; mutations in EGFR pathway genes have also been explored in relation to antiangiogenic molecules although further data are required prior to their integration into clinical practice. The introduction of immunotherapy has paved the way for a new generation of predictive markers, including genome-wide assessment of the tumor landscape. Furthermore, the development of next generation sequencing technology and non-invasive approaches to analyze circulating tumor DNA will make real-time monitoring of the tumor pharmacogenomic markers possible in the clinical routine, rendering precision medicine available to every patient.

Original languageEnglish
Article number1522
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 14 2017

Keywords

  • Anti-EGFR agents
  • Antiangiogenic molecules
  • Inflammation
  • Metastatic colorectal cancer
  • Pharmacogenomics
  • Rat sarcoma oncogene (RAS)
  • Somatic mutation
  • Targeted agents
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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