Cancer treatments are evolving. A little more than 30 years after the discovery of the genetic origin of cancer, cancer therapies have become more targeted. The last five years have seen the emergence of a new era; that of personalised medicine, which involves the individualised treatment of each patient according to the genetic and biological characteristics of his tumour. Dr. Touati Benoukraf heads the Laboratory of Bioinformatics and Epigenetics in the Cancer Science Institute (CSI) of Singapore and explains to lepetitjournal.com how research and bioinformatics work to improve treatments.
Standard treatments in personalised medicine
Dr. Touati Benoukraf – In the 1970s, researchers showed that cancer has a genetic connection, i.e. tumour cells have gene anomalies that are treated with standard cancer protocols such as radiotherapy and chemotherapy. In the 1990s, the decoding of the specific gene anomalies and the sequencing of the genes of a tumour as a whole allowed the emergence of so-called targeted therapies that aimed to kill tumour cells while sparing the normal cells of the body.
Today, for a few years now, therapies have been transitioning towards personalised medicine (also called precision medicine), whose objective is to offer specific treatments based on the tumour genome of each patient.
Bioinformatics at the service of research and medicine
TB – In this context, bioinformatics is used, thanks to “Big Data”, to harness and even produce the knowledge indispensable to the discovery of new treatments tailored to the patient.Dr. Touati Benoukraf explains how fundamental research and bioinformatics work to improve cancer treatments.
LPJ – Could you tell us your scientific background in a few words?
TB -I am from Aups, a village in South East of France, and I did my studies in Marseille, first in mathematics and computer science. But jobs in computing did not attract me much. I discovered biology while doing my masters in bioinformatics; at that time co-directed by Prof Denis Thieffry, with whom I collaborated during my doctoral thesis in bioinformatics analysis (“Analysis of the early development of the regulatory mechanisms of T cells “), and who has since become one of my main collaborators here in Singapore.
LPJ – How did you then choose to settle in Singapore?
TB -I came to Singapore for various reasons. From a personal viewpoint, I have always travelled extensively in Asia and Asia fascinates me. On the professional front, various job opportunities presented themselves and I chose to come here to work in 2010 at the Cancer Science Institute (CSI), which had already been looking towards bioinformatics and personalised medicine at a time when, in France, my work was only in the early stages.
I did two years of post-doc, before obtaining the grade of Special Fellow, thus allowing me to access significant funding for my research projects and to recruit six people for my team. It was an extraordinary opportunity for a young scientist at the beginning of his career.
LPJ – How does bioinformatics work in cancer research and the treatment of patients ?
TB -The key to cancer research is to understand gene interactions. In a few years, we have gone from the study of a single gene to the study of a group of genes in a network. As a result, the volume of data to be analysed is huge. Mathematics and computer science thus become indispensable tools in the use of this data of this scale and in the cost compatibility in the treatment of cancer patients.
For instance, the sequencing of the first human genome, which started in 1990, took around 10 years, multiple teams and several billion dollars. Today, thanks to the development of high-throughput sequencing technologies, the complete sequencing of a tumour is done in less than a week for a few thousand dollars.
The algorithms and computer software that we developed are able to analyse the numerous data from research, and they also allow us to come up with predictive models to better understand the basic mechanism developments of cells; from normal cells turning cancerous, and to establish new treatments.
LPJ – You head the Laboratory of Bioinformatics and Epigenetics. Can you tell us more about your research topics?
TB -The objective of our research is to ultimately improve the effectiveness of cancer treatments by customising them for each patient. This can be done, on the one hand, through the knowledge of the genetic signature of the cancer via the sequencing of the tumour of each patient, and on the other hand, through the knowledge of other factors, known as epigenetics, related to molecular mechanisms that modulate gene expression depending on the context.
We are interested in a particular gene, p53, because it is effectively the most frequently altered, mutated or inactivated gene in tumour cells in practically all types of cancer (except leukemia). It’s a genome “guardian”; it is involved in DNA repair and cell death. We are focusing our attention on a specific mechanism linked to its regulatory action of cell proliferation and apoptosis.
In our team there are biologists who analyse the mechanisms at the molecular level and computer scientists who analyse DNA data.
LPJ – Do the researchers have access to the genetic sequencing of tumours from real patients?
TB -Access to tumour genetic information of patients is a sensitive ethical issue, and varies according to a country’s laws. In Singapore, access to tumour samples is subject to a stringent protocol, but it is easier than in France, for example. Researchers at CSI and clinicians at the National University Hospital in particular, work in close collaboration, so that the results of the research may benefit patients, and conversely, the observations of the doctors may be communicated to the researchers. We are talking about translational medicine.
LPJ – How do you work with the French team “Computational Systems Biology” of the Institute of Biology of the École Normale Supérieure de Paris (IBENS) led by Denis Thieffry, as part of your research and the MERLION programme?
TB -Our collaboration with Denis Thieffry’s team started a few years ago. We have, among other things, organised a few workshops in Paris and Singapore. The MERLION programme was the catalyst that sped up our collaborative work.
Denis’s team specialises in the design of statistical tools and the necessary computing know-how to extract biological signals from DNA sequencing, and in the dynamic modelling of the biological regulation network. The team in particular built a “molecular interaction network” that models the biological processes involved in the action of the p53 gene by activating other genes that regulate cell proliferation and apoptosis.
We, for our part, discovered that the protein encoded by the p53 gene is also an inhibitor, i.e. it deactivates other genes in order to function. The purpose of our collaboration is to incorporate our data into the interaction network designed by the French team, which allows us to model and better understand the development mechanisms of cancerous cells.
Therapeutic interest is important. Indeed, once the mechanisms are clear, we can restore the function of the p53 gene, which is inactivated in the tumour cells, by testing new treatments aimed directly at p53-responsive genes by bypassing it.
LPJ – What is your view on the MERLION programme ?
TB -I am very satisfied with this mobility funding for researchers. We particularly appreciate the possibility of sending entire scientific delegations to France or Singapore. As a matter of fact, for multi-disciplinary projects such as ours, a physical closeness is crucial. By working together, the research progresses faster. It is equally important for us to form ties with other teams with complementary expertise and to participate in international conferences to present our results.
The budget for travel (of researchers) given by standard grants are in general very limited. The MERLION programme thus complements the other funding sources and is very useful. It gives the possibility to initiate, or in our case, to consolidate franco-singaporean collaborations with the aim of expediting scientific advances.
Original article written and released in French by Cécile BROSOLO (www.lepetitjournal.com/singapour), July 1, 2016, translated by Audrey TAY, Institut Français Singapore.