RG17: From Tumour Biology to Cancer Therapies

RG17 is a translational team working in hemato- and gynecologic pathology, breast and brain tumours, genetic and epigenetic regulation, and microenvironment. Despite different backgrounds and expertise (basic and clinical) our work is based on similar approaches. In alignment with our practice, we integrate several European networks with access to a large number of annotated patient samples, being highly involved in cooperative trials for therapeutic development (from identification to testing). We aim to increase our research output with solid collaborative work mainly in cancer biology and microenvironment to develop new therapeutic targets while taking advantage of IPOLFG Tumour Bank.

We study the role of tumour microenvironment in in vitro/in vivo cancer models and in patients' samples (tumour, normal tissue, body fluids) to determine the role of extracellular matrix and non-tumour bystander cells in signal transduction, migration/invasion and differentiation; and to unveil cancer type-specific metabolic mechanisms of adaptation, since the endogenous metabolism conditions drug response causing chemoresistance and disease recurrence. We are also interested in the genetic profile and epigenetic modulation of cancer cells, and in the identification of potentially oncogenic aberrant protein isoforms and their expression dynamics upon epigenetic modifiers and conventional therapy.

Specific aims:

To develop new markers with clinical value while better understanding the biological mechanisms of carcinogenesis;
To integrate European epidemiological networks to improve national clinical databases;
To characterize tumour intra- and inter-clonal diversity and anti-tumour host response, including immunological and vascular components;
To identify key metabolic players in therapy response and cancer type-specific;
To reinforce our presence in international networks via comprehensive research projects, including translational academic clinical trials (i.e. early phases).

Keywords: Tumour microenvironment; Targeted therapies; Tumour genetics; Gyneacological/Hematological/Brain/Breast-Cancer

Latest Publications

Guzella TS, Barreto VM, Carneiro J (2019) Partitioning stable and unstable expression level variation in cell populations: a theoretical framework with application to the T cell receptor. bioRxiv

Vicente MM, Mendes A, Cruz M, Vicente JR, Barreto VM (2019) A CyclinB2-Cas9 fusion promotes the homology-directed repair of double-strand breaks. bioRxiv

Rebelo SP, Pinto C, Martins TR, Harrer N, Estrada MF, Loza-Alvarez P, Cabeçadas J, Alves PM, Gualda EJ, Sommergruber W, Brito C (2018) 3D-3-culture: a tool to unveil macrophage plasticity in the tumour microenvironment. Biomaterials 163:185-197

Rito M, Mitani Y, Bell D, Mariano FV, Almalki ST, Pytynia KB, Fonseca I, El-Naggar AK (2018) Frequent and differential mutations of the CYLD gene in basal cell salivary neoplasms: linkage to tumor development and progression. Modern Pathology 31:1064–1072

Nunes SC, Ramos C, Lopes-Coelho F, Sequeira CO, Silva F, Gouveia-Fernandes S, Rodrigues A, Guimarães A, Silveira M, Abreu S, Santo VE, Brito C, Félix A, Pereira SA, Serpa J (2018) Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity. Scientific Reports 8(1):9513