The identification of key events during tumour development has led to innovative therapeutic approaches targeting critical defective pathways. However, the exclusive targeting of mitogenic mechanisms has shown two crucial limitations: the emergence of chemo-resistance within target cells and evasion promoted by tumour heterogeneity.

In this context, the Foundation Synergie Lyon Cancer aims to promote clinical, translational and fundamental research teams focused on testing innovative therapeutic approaches designed specifically to target cancerous cell survival processes. This approach has the advantage of targeting processes involved during the critical phases of tumour progression: the initial phase of carcinogenesis, invasion and metastasis, acquisition of chemo-resistance and tumour stem-cell survival.

Cell Senescence, Apoptosis and Tumour Escape

In vitro and in vivo, the inhibition of cellular senescence processes and apoptosis is required for malignant transformation. A large body of evidence shows that this inactivation plays a crucial role both during the early phases of cancerogenesis and during two stages of tumour development, which have a major impact on the prognosis of cancerous pathologies: metastastic diffusion and chemo-resistance. Several teams involved in the Foundation’s network have demonstrated specific mechanisms that allow tumour cells to escape these cell-saving systems. Approaches seeking to restore these mechanisms are currently being sought. Within the Synergie Lyon Cancer framework, the teams involved have structured their work to identify recurrent senescence inactivation mechanisms and apoptosis, to look into their influence on metastatic and chemo-resistant diffusion processes and to optimise the target validation and pre-clinical model generation stage.

Immune surveillance and Tumour Escape

The immune system contributes to the protection against tumours through a process called immuno-surveillance. However, the immune system can facilitate tumour progression through different mechanisms such as the production of cytokines (pro-angiogenic or anti-apoptotic growth factors) or the induction of immune tolerance (alteration of the physiology of dendritic cells [DC], suppressor lymphocytes [Treg]). Innovative targeted therapies such as monoclonal antibodies and vaccines can restore immune surveillance against tumours.

Two research themes are being developed as a priority:

- identification of escape mechanisms from immune response (endogenous or induced by therapy) and the molecular alterations involved.

- development of strategies to restore a therapeutic anti-tumoral immune response using a synergistic approach combining induction of tumour cell apoptosis and stimulation of the immune system.