Pharmacological profile and pharmacogenomics of anti-cancer drugs used for targeted therapy

Raffaele Di Francia, Angela De Monaco, Mariangela Saggese, Giancarla Iaccarino, Stefania Crisci, Ferdinando Frigeri, Rosaria De Filippi, Massimiliano Berretta, Antonio Pinto

Research output: Contribution to journalReview articlepeer-review

Abstract

Background: Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors. Objective: This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance of either individual gene polymorphisms or acquired mutation in a cancer cell. In addition, an early outline evaluation of the genotyping costs and methods has been taken into consideration. Future Outlook: To date, therapeutic drug monitoring (TDM) of mAbs and SMIs is not yet supported by heavy scientific evidence. Extensive effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomized trials of classic dosing versus PK-guided adaptive dosing. The detection of individual pharmacogenomics profile could be the key for the oncologists that will have new resources to make treatment decisions for their patients in order to maximize the benefit and minimize the toxicity. Based on this purpose, the clinician should evaluate advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacological approach to performing a tailored therapy.

Original languageEnglish
Pages (from-to)499-511
Number of pages13
JournalCurrent Cancer Drug Targets
Volume18
Issue number5
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Anticancer mAbs
  • Cancer cell
  • Personalized medicine
  • Pharmacogenomics
  • Tailored therapy
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Cancer Research

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