Cancer Development and innate immune evasion
Tumor cells in order to thrive employ mechanisms that circumvent the immune response. This dynamic process is explained by the concept of cancer immunoediting, where some tumor cells variants have the capacity to escape the innate and adaptive immune system recognition, to then expand and hijack the host. However some tumor variants may protect less fit clones enabling immune evasion to then contribute to the whole tumor fitness, generating heterogeneous tumors with clones with different tumor traits. By combining live imaging, genetic and chemical tools we are studying the process of innate immune evasion and intra-tumoral clonal interactions using the zebrafish-larvae xenograft model. Understanding the process of innate immune rejection/ evasion may lead to new avenues of anti-cancer therapies based on modulating conserved innate immune mechanisms.
Zebrafish Avatars, towards personalised medicine
Despite advances in targeted cancer treatments, we still lack methods to predict how a specific cancer in a specific patient will respond to a given therapy. Consequently, patients go through rounds-of-trial-and-error approaches based on guidelines to find the best treatment, often subjected to unnecessary toxicity. We are developing zebrafish Patient Derived Xenografts (PDX) or “Avatars”, as sensors for cancer behavior and personalized therapy screening (Fior et al, PNAS 2017).
In collaboration with Miguel Godinho Ferreira, IRCAN – Nice, the Champalimaud Clinical Centre and the Hospital Amadora Sintra, we are testing the predictiveness of this assay in CRC and Breast Cancer, by comparing the therapeutic response obtained in patients with their matching zebrafish Avatars.
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