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Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. These new tools have profoundly changed therapeutic management in oncology, with increasingly precise molecular characterization of tumors leading to increasingly personalized therapeutic targeting. Detection of circulating tumor cells and/or circulating tumor DNA in blood samples -so-called 'liquid biopsies'- can now provide a genetic snapshot of the patient's tumor through an alternative and less invasive procedure than biopsy of the tumor tissue itself. This procedure for characterizing and monitoring the disease in real time facilitates the search for possible relapses, the emergence of resistance, or emergence of a new therapeutic target. In the long term, it might also provide a means of early detection of cancer. These new approaches require the treatment of ever-increasing amounts of clinical data, notably, with the goal of calculating composite clinical-biological predictive scores. The use of artificial intelligence will be unavoidable in this domain, but it raises ethical questions and implications for the health-care system that will have to be addressed., Les progrès technologiques, en particulier le développement du séquençage à haut débit, ont conduit à l’émergence d’une nouvelle génération de biomarqueurs tumoraux moléculaires. Ces nouveaux outils ont profondément modifié la prise en charge thérapeutique en oncologie avec une caractérisation moléculaire de plus en plus précise des tumeurs amenant à un ciblage thérapeutique personnalisé. La détection des cellules tumorales circulantes et/ou de l’ADN tumoral circulant dans des prélèvements sanguins, encore appelés « biopsies liquides », peut désormais fournir un instantané du profil génétique de la tumeur du patient grâce à une procédure alternative et moins invasive qu’une biopsie du tissu tumoral lui-même. Cette méthode de caractérisation moléculaire et de suivi de la maladie en temps réel facilite la recherche d’éventuelles rechutes, de l’émergence de résistances ou d’une nouvelle cible thérapeutique. À long terme, les biopsies liquides pourraient également fournir un moyen de détection précoce du cancer. Ces nouvelles approches nécessitent le traitement d’une quantité, toujours croissante, de données, en particulier cliniques, notamment dans l’optique d’élaborer des scores clinico-biologiques composites. L’utilisation de l’intelligence artificielle est un outil d’avenir dans ce domaine, mais elle soulève des questions éthiques et des implications pour l’organisation du système de santé qui devront être abordées. more...

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria. more...

Metastasis suppressor genes - unlike tumor suppressor genes - are defined by their capacity to control metastatic dissemination in vivo without affecting growth of the primary tumor. The first of these metastasis suppressor genes, NM23, was identified in 1988. Since then, expression of NM23 has been studied widely in human tumor cohorts, often with contradictory results. Not only is NM23 overexpressed in most human solid tumors when compared to healthy tissues, but also low expression of NM23 correlates with metastasis and poor clinical prognosis in the advanced stages of a number of epithelial cancer types, including melanoma, breast, colon, and liver carcinoma. This does not hold true, however, for other cancer types such as neuroblastoma and hematological malignancies, in which high NM23 expression correlates with more aggressive disease. Genetic alterations in the NM23 gene - loss of heterozygosity, spontaneous mutations and polymorphisms - are rarely found in tumors; thus, the metastatic potential of tumor cells is probably affected by NM23 protein levels. Three lines of evidence demonstrate the anti-metastatic activity of NM23: first, overexpression of NM23 in metastatic cell lines reduces their metastatic potential in xenograft models; second, the incidence of lung metastases is elevated in NM23 knockout mice prone to develop hepatocellular carcinoma, and, third, silencing NM23 by RNA interference confers a "metastatic phenotype" on non-invasive human epithelial liver and colon cancer cell lines. It appears that NM23 is crucial for inhibiting invasive migration, so acting at early stages of metastatic dissemination. The mechanistic basis of the metastasis suppressor function of NM23 and its regulated expression still remains obscure, however. Reactivation of expression of the endogenous NM23 gene in tumor cells, or stimulation of the pathways it controls, constitutes a promising avenue for anti-metastatic therapy. more...

Metastatic dissemination represents a leading cause of death in cancer patients. Elucidating the mechanisms of the metastatic process is therefore essential to control it. Since 1988, when the NME (NM23) gene was discovered, several genes specifically suppressing the metastatic potential of tumor cells, have been identified. These metastasis suppressor genes, which exhibit a reduced expression in metastatic tumor cells, are defined by their capacity to suppress metastatic dissemination in vivo without inhibiting primary tumor growth when transfected into metastatic cell lines and injected into experimental animals. Their decreased expression in a subset of human tumor cohorts is associated with a high metastatic potential, thus confirming the data obtained in experimental models. Most of these genes affect key signal transduction pathways, including mitogen-activated protein kinases, Rho-GTPases and G-protein-coupled receptors. These signaling categories control cell-cell and cell-matrix interactions, which are important in monitoring adhesion, invasion and migration properties of metastatic tumor cells. Reduced expression of metastasis suppressor genes is most often due to epigenetic mechanisms, suggesting that their re-expression could constitute a new anti-metastatic therapy. In this paper, we review the literature on metastasis suppressor genes, with a particular focus on NM23. more...