open access: PLOS ONE: Drug Cocktail Optimization in Chemotherapy of Cancer

 Blogger's Note: focus is on leukemia however many drugs discussed are used in other cancers including solid tumors

PLOS ONE: Drug Cocktail Optimization in Chemotherapy of Cancer

Background

In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP). Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency.

Objective

The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy.

Data sources and methods

Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract.

Results

We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemoth​erapy.

Editor: Daotai Nie, Southern Illinois University School of Medicine, United States of America
Received: August 6, 2012; Accepted: October 29, 2012; Published: December 7, 2012

Funding: This work was supported by Berliner Krebsgeselleschaft, DFG Graduate School 1776, BMBF MedSys, EU SynSys. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.