The RCSI Centre for Systems Medicine will host a seminar by Dr Pavel Souček (NIPH, Prague) on the molecular mechanisms of responses to major anticancer drugs by
Dr Pavel Souček
Head, Toxicogenomics Department & Group for Biotransformations, Centre of Occupational Medicine, National Institute of Public Health (NIPH), Prague, Czech Republic
Pharmacogenomics of breast, colorectal, and pancreatic carcinomas
Abstract: Response to anticancer therapy on the molecular level is limited by the inter-individual variability in drug metabolizing enzymes (e.g. cytochromes P450) and transporters as ATP-binding cassette (ABC) transporters or solute carrier (SLC) proteins. We followed associations of clinical features, including therapy outcome, with gene expression of more than 100 genes from pathways active in metabolism and transport of major anticancer drugs (anthracyclines, antimetabolites, taxanes) in sets of tumor and non-neoplastic tissues from breast, colorectal and pancreatic carcinoma patients.
We have found potential biomarkers of patient´s prognosis, e.g. ABCC11 in colorectal (Hlavata et al. Mutagenesis 2012) or ABCA12, ABCA13, ABCC1, ABCC8, and ABCD2 in breast carcinoma (Hlavac et al. Pharmacogenomics 2013). The observed, overexpression of multidrug-resistance connected exporters (ABC transporters) and downregulation of drug importers (SLCs) in pancreatic adenocarcinomas may contribute to the generally low treatment response of this cancer and suggests new drug targets (Mohelnikova-Duchonova et al. Pancreas 2013 and Cancer Chem Pharmacol. 2013).
Marked differences in expression profiles suggest that the followed carcinomas may differ in mechanisms of drug resistance. We are currently performing validation and mechanistic studies to verify the importance of the revealed biomarkers for cancer outcome.
All are welcome to the Nightingale Theatre, RCSI 123 St Stephen’s Green on Tuesday August 26th at 4pm.
This seminar is supported by HRB funding to Dr David Hughes in the CSM