Four areas of research to address all facets of the biology of cancer

Valérie Devillaine
At the Research Center, the 12 mixed research units are organized into four fields based on natural scientific interactions and strong medical potential. The Translational Research department operates as a powerful catalyst for medical-scientific programs.
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The scientific challenges faced require multiple skills as well as efficient sharing of information through stimulating forums for exchange among specialists. The scientific project is created within the scope of this sharing among disciplines, encouraging original collaborations in four fields.

Each research field is addressed according to multiple facets, from basic research to application research, with the same requirements in terms of integrity and scientific quality. This dynamic gives rise to new ideas. It also guarantees that society’s knowledge will improve considerably and will help put discoveries into action by converting them whenever possible to applications for innovative technologies and optimum quality of care.


Field 1: Biology & Chemistry of Radiations, Cell Signaling and Cancer

There are 16 research teams in this field, spread out among three units at the Orsay site. These biologists, chemists and physicists are seeking to decipher the mechanisms involved in the development of cancer and the metastatic process, as well as to develop new cancer-fighting therapeutic approaches. They are studying the mechanisms used by the cells to preserve the integrity of their genome, in physiological conditions and in response to various genotoxic stresses, such as ionizing radiation and UV rays. They are also focusing on cellular actions and reactions that take complex paths, such as intracellular signaling pathways, on the processes of development of tissues from embryonic stem cells, and on cell and tissue modifications during tumorigenesis (in particular, for melanoma and pediatric tumors).

Lastly, the teams are developing new molecules to treat cancers, among other things using a chemical library with over 9,000 chemical compounds, and new technologies, particularly in bio-imaging, to study the effects of new medications.

The knowledge thus acquired was used to design molecules that sensitize tumors to radiotherapy, known as Dbaits. These radiotherapy boosters were used in a clinical trial for melanoma, which was successfully concluded. They continue to be studied to extend their use to other cancers, as well as to discover other molecules that can increase the effectiveness of radiotherapy. Other efforts have helped to reduce the side effects of radiotherapy by modifying the radiation protocol to deliver the radiation dose in a very short time. These “flash” radiation doses now feature heavily in research, especially in proton therapy.


Field 2: Development, Cancer, Genetics and Epigenetics

The aim in this field is to further fundamental knowledge of physiological processes during normal development. It is based on the simple but essential idea that understanding normal mechanisms during development enlightens us on the pathological mechanisms, since cancerization is a result of multiple disturbances in the mechanisms that are normally involved in the development, proliferation and identity of cells.

Researchers are also looking into the stability of the genome, its replication, its repair and its epigenetic plasticity. This field of research involves 19 teams across three units in Paris.

Recently, work in this field has revealed the influence of the epigenome on the transmission

 of genetic information during cell division, and has established a new spatial organization rule for chromosomes that reflects their functioning. It has also allowed new-generation sequencing techniques to be introduced into clinical applications for prostate cancer and cervical cancer.

These activities use multiple approaches, some of which are at the frontier between biology and physics. They explore varied models: cell, animal, and human biological samples.


Field 3: Integrative Tumor Biology, Immunology and Environment

The principle of integrated biology is to study a living thing in its ecosystem, to observe the cell in its environment, and to understand its interactions within an organism. This field is flourishing at present. The first clinical success stories in immunotherapy call for improving basic knowledge on the links between cancer and immunity. This is true for cells, tissues, living organisms and populations.

Researchers in this field, with 17 teams spread throughout three units, are working to understand the main principles of the etiology, genesis and progression of cancer. They consider cancer to be a complex ecosystem, where a number of different cell components interact and govern the development of the pathology within the patient’s specific genetic context: the cancer cells themselves, the tumor’s microenvironment and the immune system. They are based on the direct study of malignant human tumors and on experimental models. They are also trying to better understand immunological responses to tumors, and to learn how to use the immune system to fight cancer. In addition to basic research, this field is very much anchored in translational research and development of clinical trials.

This approach is assisted by new tools in bioinformatics and big-data processing, and modeling of interactions between genes or between cells in the form of complex networks. They recently modeled the transition between epithelium and mesenchyme, which leads to the formation of metastases in mice.


Field 4: Multiscale Physics-Biology-Chemistry and Cancer

There are no fewer than 30 teams in this field, working in three units. These teams all use interdisciplinary approaches involving physics, chemistry and biology to develop basic knowledge in cellular biology and innovative tools for biomedical research. Through this broad spectrum of approaches, researchers look at the space and time of cells and tissues (from electronic microscopy to in-vivo imaging, and tracking of isolated molecules for a few milliseconds or migration of cells over several hours).

They can thus reveal the mechanical effects of physical parameters, such as membrane pressure and tension on the behavior of normal or cancer cells, or exploit the potential of synthetic chemistry to create unique molecules with biological and medical potential.

In this field, Institut Curie has recently uncovered the role of ESCRT cell machinery in the repair of plasma membranes and nuclear membranes. Its researchers have also identified the point of division between the red and white lines of blood cells, and discovered the effect of mechanical pressure that tumor growth places on a signaling pathway.

On a more applied scale, they have revealed new therapeutic screening approaches involving immunotherapy and anti-tumor conjugates.


Translational Research: a catalyzer of discoveries

The aim of the Translational Research department is to accelerate the process that leads from scientific innovation to better care for patients. In concrete terms, it brings doctors and researchers together to accelerate transitioning from basic research discoveries to clinical applications. It has five dedicated technological platforms and houses six teams at the Inserm or CNRS units, five of which also receive support from the INCa (French

national cancer institute) through SiRIC financing, and three translational groups.

The department also helps researchers to promote their discoveries through partnerships with industrial players preferred by our Institut Carnot certification, or by filing patents or creating new companies.

One of the examples of research conducted in this department concerns uveal melanoma; the department was able to provide proof of concept for the therapeutic potential of new drugs. These candidate medications are now in clinical trials sponsored by Novartis and for which Institut Curie is the principal investigator.

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