PROJECTS

Cancer Development and innate immune evasion

Immunotherapy is a revolutionary approach to cancer treatment. However, many patients do not respond and the potential for serious side effects exists. Therapy often fails because tumor cells are not recognized (they turn invisible) or because of other immune suppressive mechanisms in the tumor microenvironment that further block therapy. To generate more effective responses to checkpoint immunotherapy it is critical to select patients that will benefit from therapy (the right patients) but also discover new compounds that can help fully unleash the immune response i.e or take out the “invisibility cloak” or block the other suppressive mechanisms that avoid the “good cops” from acting. By taking advantage of the zebrafish xenograft model the Fior Lab is focusing on understanding the molecular players involved in this rejection/ suppression process and discover new therapies to be combined with adaptive immunotherapy.

Zebrafish Avatars, towards personalized 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, Costa&Ferreira et al, EBiomedicine 2020, RAlmeida et al CommBiology, 2020, Varanda & Logrado et al, Cancers 2020, Costa&Estrada et al, Cells 2020).

In collaboration with 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.

(cartoon by GilCosta design)