Scientific challenges

The Institute has three research objectives: identification of risk factors, redefinition of cancers depending on the biological signature of each tumor profile, tailored to the diagnosis, and development of a personalized drug based on the patient’s and his/her cancer’s profile.

Genomics

Extraction of a DNA fragment from agarose gel in the laboratory of the

Extraction of a DNA fragment from agarose gel in the laboratory of the "Epithelial cells, angiogenesis and signaling" department of Inserm Unit 858, Rangueil University Hospital, Toulouse

The development of microarray techniques currently enables genetic alterations and genetic expressions within the genome to be analyzed. Thanks to the precision of these methods, a considerable number of new molecular events associated with the specific or non-specific tumorigenesis processes of each cancer have been identified. Moreover, these analyses mean that a more precise "geno/phenotyping" of tumors than former anatomopathological classifications is possible. Accordingly, by studying genetic alterations in cells from a tumor, it should be possible to identify networks of critical genes for carcinogenesis, model new diagnostic and prognostic tools and define the best therapeutic strategies by determining the predictive markers of response to a treatment. France has also committed to an international program aimed at sequencing all tumor genomes.

Proteomics

For a pertinent understanding of the somatic alterations in a cancer, it is essential to look to the analysis of proteins, which are the real biological effectors. "Proteomics" becomes the main component of so-called post-genomic approaches. But the performances (resolution, sensitivity, reproducibility, reliability, flow, etc.) of these approaches are still limited, and even insufficient to identify and quantitatively quantify minor proteic markers in a reproducible and reliable manner from as complex biological fluids as blood. The clinical implementation of these tools, “at the patient’s bedside”, is therefore premature and requires rigorous evaluation.

Tumoral microenvironment

In addition to the physiological characteristics of tumor cells, the components of the tumoral environment (stroma cells, immune system cells and endothelial cells of the neovessels) are now recognized as being important for understanding carcinogenesis and are becoming new therapeutic targets. Although research into cancer immunology is widely developed in France, a new research field, incorporating all of these factors, is fast emerging. The primary objective is now to understand the relations between host and tumor and the interactions between tumor cells and immune system cells for example.

Targeted therapy

Blood test on a patient with a flow cytometer. Inserm Unit 891

Blood test on a patient with a flow cytometer. Inserm Unit 891 "Research Center in Cancerology” in Marseilles, Institut Paoli-Calmettes, Marseille

While cytotoxic chemotherapy only targeted global cell proliferation, targeted chemotherapy targets the actual mechanisms of oncogenesis. The targeted molecules are determined depending on whether a target is present, its activation state and its primary or secondary role in the genesis of the tumor in consideration. Moreover, it is now known that: 1) the presence of certain mutations on one target can predict sensitivity, and on another, resistance; 2) the medicinal dose can overcome some resistances but not others; 3) changes in molecular alterations must be considered when treating relapses. The existence of these new therapies is therefore triggering an overhaul of medical oncology practices in favour of individual prescriptions (personalized drugs), based on the biological parameters of the tumor and patient.

Imaging

Research is being geared more towards optimizing molecular imaging techniques. These combine the conventional medical imaging techniques with the use of tracers that are able to pinpoint a specific cell signal. This makes it possible to visualize the phenomenon of interest in vivo without intrusive action. As such, imaging by X-rays, ultrasound and MRI helps to quantify the progressive potential of numerous tumors, evaluate sensitivity to treatments early on and identify residual tumor masses. PET (positron emission tomography), with the use of new radiopharmacological markers of cell division, angiogenesis and hypoxia, is also playing a key role in the functional evaluation of human tumors and their treatments. In tumor imaging, the role of biotechnologies is therefore increasing and multidiciplinarity ensures swift progress in this regard.

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