The role of pharmacogenetics and pharmacogenomics in 21st-century medicine: state of the art and new challenges discussed in the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF)

The rapid advancements made in the field of pharmacogenetics and pharmacogenomics triggered by the creation of large human genetic and epigenetic international projects, the formation of international consortia, and the identification of novel biomarkers of drug response were recently discussed in the VII Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF) Conference. Biannually, the SEFF organizes a conference where experts meet to present and discuss the latest developments in the field. This year, the seventh conference of the society was held on April 20–21, 2015, in Madrid, at the Spanish National Cancer Research Centre and was organized by Luis Lopez-Fernandez, Anna Gonzalez-Neira, and Cristina Rodríguez-Antona, with the help of a scientific board of well-known national experts in pharmacogenetics. This year, the conference was divided into four symposia where new advances in personalized medicine and work strategies were presented: (1) human genetics: international projects and new technologies; (2) new advances in pharmacogenetics: consortia and novel working strategies; (3) the pharmacogenetics as a tool in cancer treatment; and (4) implementation of pharmacogenetics in the clinic. Within this framework, more than 110 experts discussed the state of the art and the new challenges ahead in these fields of knowledge, 21 invited lectures were presented by speakers belonging to different Spanish institutions, two plenary lectures were given by internationally renowned experts in the field, and 10 short oral presentations and 25 posters were presented. This year, the keynote presentations by internationally renowned experts in pharmacogenetics included the intervention of Munir Pirmohamed, from the Institute of Translational Medicine (Liverpool, UK), and Howard McLeod, from the Moffitt Cancer Center (Tampa, FL, USA). The SEFF Conference provides a fruitful meeting place where synergistic interactions are established. The VII SEFF Conference has served as the basis for four mini-reviews published in this issue of Drug Metabolism and Personalized Therapy discussing different topics described below.

Recently, a very impressive achievement has been made regarding the availability of whole exomes and genomes, which are contributing to a much better understanding of human genetic variation and to the identification of variants associated with human diseases and complex phenotypes (including drug response). In this regard, the critical step has been the development of massively parallel sequencing technologies, which allow sequencing of an entire genome in less than a day in a cost-effective manner. This next-generation sequencing (NGS) technologies are the basis for international projects such as the 1000 Genomes Project [1] and the Genotype-Tissue Expression project [2]. NGS technologies have also contributed to the rapid increase of epigenetic studies, adding one more layer to the genetic information [3].

The field in which pharmacogenomics is probably having the most prominent role is oncology. Here, the lack of efficacy and the toxicity of the therapeutic agents are among the major obstacles for improving survival and quality of life of cancer patients. These problems are critical because most anticancer drugs are only effective in a minority of patients and the narrow therapeutic indexes of these drugs frequently lead to severe toxicities or even death [4]. In this context, defining therapy decisions tailored individually to patients sharing molecular characteristics can improve therapeutic response and minimize adverse effects. The Cancer Genome Atlas is an example of the new advancements brought by NGS. This is a large international comprehensive study that has characterized samples from 11,000 cancer patients across 33 different tumor types through the application of omic technologies. Now, the Pan-Cancer Analysis of Whole Genomes, in collaboration with the International Cancer Genome Consortium, will analyze whole genome data from 2000 pairs of tumor and normal samples and integrate the results with clinical and other molecular data available [5].

This new genetic and epigenetic knowledge has the potential to constitute the basis for a more efficient personalized medicine. However, the challenge ahead will be the interpretation of this massive omic information and exploit it for clinical benefit, including improvement in response prediction by identifying, among the millions of variants that are being detected, the relevant alterations [5–7]. In this respect, a major limitation in pharmacogenomics is the difficulty to establish accurately the utility of the identified markers for patients and health-care systems. The possibility of conducting prospective pharmacogenetic-guided clinical trials is limited or impracticable for many drugs. Even conducting retrospective pharmacogenomic projects including large numbers of samples from patients homogenously treated with the same drug and with detailed clinical data are challenging. In this regard, the creation of national and international pharmacogenomics consortia can play a critical role, being able to pull together in a collective effort large numbers of homogenous and well-characterized samples that are needed to produce the level of evidence required to establish that a marker is clinically useful and should be introduced for routine use. Thus, the implementation of pharmacogenetics counts with important obstacles, but there are also opportunities and several recent examples of success.