Title:Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy
Volume: 18
Issue: 5
Author(s): Raffaele Di Francia*, Angela De Monaco, Mariangela Saggese, Giancarla Iaccarino, Stefania Crisci, Ferdinando Frigeri, Rosaria De Filippi, Massimiliano Berretta and Antonio Pinto
Affiliation:
- Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples,Italy
Keywords:
Anticancer mAbs, personalized medicine, pharmacogenomics, tailored therapy, tyrosine kinase inhibitors, cancer cell.
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.
