Research Sections

Section of Mechanisms of Carcinogenesis

Cancers are the consequence of combined genetic and epigenetic changes induced by environmental factors that trigger inappropriate activation or inactivation of specific genes leading to neoplastic transformations. Although there is consensus that exposure to environmental factors accounts for over two thirds of cancers, meaning the majority of cancers are potentially avoidable, there is a paucity of evidence regarding the critical molecular events that occur in early stages of cancer development or in precursor lesions as well as environmental factors and endogenous cues that trigger these changes.

In addition, the challenge posed by numerous sequencing efforts, is to identify the deregulated genes/pathways and changes in the genome and epigenome that precede and promote tumour development, and to differentiate functionally important (“drivers”) from non-functional “passenger” events. The spectacular advances in epigenomics and the emergence of powerful technologies that allow the analysis of the genome and epigenome with unprecedented resolution in both high throughput and genome-wide settings have dramatically accelerated investigations in the area of cancer research and molecular epidemiology. These advances have opened the exciting possibility of simultaneously identifying multiple changes affecting the genome and epigenome of normal, precursor and cancer cells as well as their link to the environment. Therefore, it will now be possible to improve our understanding of the mechanisms underlying cancer development and progression. It will also be possible to define which genetic and epigenetic alterations, or combinations thereof, can be interpreted as reliable biomarkers of exposures. By identifying changes in the genome and epigenome (genetic and epigenetic signatures) associated with tumour cells and surrogate tissues associated with specific known and suspected environmental risk factors, it may be possible to identify particularly high risk individuals and potentially design an efficient strategy for cancer prevention.

Future directions and strategic vision

The broad long-term goal of the Mechanisms of Carcinogenesis Section (MCA) is to advance understanding of mechanisms of carcinogenesis and to contribute to cancer prevention. This is achieved through investigating interactions between the genes, the epigenome and the environment. MCA conducts mechanistic studies aiming to discern the mechanisms by which genetic and epigenetic modifications dictate cancer development and progression. In addition, in collaboration with epidemiology Groups, the Section contributes to the development of translational studies through the discovery and validation of biomarkers of tumorigenesis and environmental exposures. Another focus of MCA is the development of genetic/epigenetic methods that are applicable to biobanks associated with case-control and population-based studies.

Several recent advances have resulted in exciting opportunities for cancer research in understanding the mechanisms of cancer development. These include: (i) the completion of the major international sequencing initiatives (including The Cancer Genome Project) and the availability of extensive repositories of gene mutations in a wide range of human cancers and genetic variants, (ii) accessible and cheaper profiling techniques, and (iii) the availability of a large series of biospecimens from population-based cohorts, including the IARC biobank and those collected in low- and middle-resource countries. MCA brings together internal and external Groups with different expertise and research tools and promotes synergies among existing programmes at IARC and international collaborations, thus yielding added value to existing programmes.

The Section comprises two Groups: the Molecular Mechanisms and Biomarker Group (MMB), and the Epigenetics Group (EGE), both of which work in close collaboration with the aim to create synergies and better exploit and further expand unique research tools and expertise. Both Groups also promote collaboration between laboratory scientists and epidemiologists as well as between different programs at IARC, making a unique contribution and bringing added value to IARC scientific activities, consistent with the IARC Medium Term Strategic Vision.

MCA has an essential and timely role to play in studies aiming to advance our understanding of molecular mechanisms underlying carcinogenesis and in developing strategies to reduce the cancer burden. Future research activities of the Section will be guided by the following criteria: (i) scientific quality, (ii) potential contribution to better mechanistic understanding of tumorigenesis, (iii) potential contribution to biomarker discovery and cancer prevention, (iv) potential to promote international collaboration and synergize with major IARC programmes including those in epidemiology (molecular epidemiology), and (v) complementarity with, and potential to yield an additional value over existing national programmes.

The Section receives funding from the European Union, the National Institute of Health / National Cancer Institute (USA), the Institut National du Cancer (INCa), France and from international and national cancer charities (Association pour la Recherche sur le Cancer (ARC), France, the Ligue Nationale Contre le Cancer, France, and Swiss Bridge).