Where Ideas Grow

Liga Portuguesa Contra o Cancro rewards five young researchers

The common trait of five of the 16 projects rewarded this year with scientific research grants in oncology awarded by the Liga Portuguesa Contra o Cancro – Núcleo Regional do Norte (LPCC-NRN) is that they are promising studies in the fight against cancer and will be conducted over the next year by young researchers from i3S.

Aimed at young researchers from scientific institutions in the North Region, these scholarships are designed to support innovative research projects in the area of oncology through individual funding of 12,600 euros. The i3S projects focus on pediatric tumors (Bárbara Ferreira), circulating tumor cells (Guilherme Faria), lymphomas (Liliana Arede), prostate cancer (Sílvia Soares), and colorectal cancer (Ricella da Silva).

Developing ex-vivo organoids to treat pediatric brain tumors

The work presented by Bárbara Ferreira, under the guidance of researcher Jorge Lima, focuses on the study of pediatric tumors of the central nervous system - namely their molecular biology and the translation of this knowledge into clinical practice with the aim of finding more personalized and effective therapies with fewer side effects.

In collaboration with the Centro Hospitalar Universitário São João, the team from the Cancer Signaling and Metabolism group is developing an innovative pre-clinical model: ex-vivo organoids derived from surgical material from pediatric brain tumors, capable of growing and maintaining molecular characteristics of their tumors of origin. The project, explains Bárbara Ferreira, “has as its main objective to determine the profile of a set of proteins, the kinases, which are activated. In this way, it will be possible to identify which cell signaling pathways contribute to the growth and progression of these tumors and which may constitute potential therapeutic targets for their treatment”.

This project follows on from a national study called PRECISEKIDS, led by Jorge Lima, which aimed to determine the genetic profile of pediatric brain tumors, providing crucial molecular information for the diagnostic process and therapeutic choice. “The implementation of ex-vivo organoids as a preclinical model and their molecular characterization is a fundamental step for these patients to have access to a personalized therapeutic approach, reducing the adverse effects associated with treatments and increasing their quality of life”, adds Bárbara Ferreira. This LPCC grant represents “recognition of the potential and relevance of our project”.

Studying the glycans of circulating tumor cells

What is the role of glycans in circulating tumor cells (CTCs) and in tumor metastasis? These are the main questions intended to be answered by Guilherme Faria’s project, under the guidance of researcher Salomé Pinho from the Immunology, Cancer & GlycoMedicine group. To this end, the researcher will focus on the layer of sugars (glycans) that exist on the surface of circulating tumor cells (CTCs) - and more specifically on those cells descended from the primary tumor and which are responsible for the formation of new metastatic foci.

“We know that these sugars (glycans) are crucial for the immune escape that occurs in the primary tumor and so we intend to understand their relevance for the survival of CTCs and for their metastatic dissemination, with a particular focus on the interaction with the immune system”, explains Guilherme Faria. Another objective, he adds, “is to determine whether the glycosylation patterns of these cells may have clinical relevance, providing predictive information for the purposes of stratifying the risk of metastasis or selecting personalized therapies”.

Increasing the effectiveness of CAR-T cell immunotherapy through low-dose radiotherapy

When transplanted, CAR (Chimeric Antigen Receptor)-T cells, used in immunotherapy, adhere to the vascular endothelium and migrate to tumor tissue, where they interact with malignant cells. Thus, interventions that restructure blood vessels and endothelial cells can significantly affect the performance and effectiveness of CAR-T cells in their effect on tumor elimination.
The proposal presented by Liliana Arede, from the Hematopoiesis and Microenvironments group led by Delfim Duarte, intends to investigate the role of low-dose radiotherapy in remodeling the vascular microenvironment of lymphoma, and consequently, in helping the CAR-T cells to recognize and destroy tumor cells more easily.

The award of this grant, underlines Liliana Arede, “is, without a doubt, a strong incentive for completing this study, which will be carried out in collaboration with IPO-Porto in the context of the Porto Comprehensive Cancer Center and which we believe may improve the prognosis of many cancer patients undergoing immunotherapy with CAR-T cells”.

Gold nanoparticles to improve prostate cancer treatment

Radiation therapy is one of the most commonly used approaches to treating prostate cancer, but about 50 percent of patients experience a recurrence after five years. It is essential to optimize the treatment in order to increase the radiosensitivity of cancer cells and thus reduce the risk of recurrence and metastasis. Based on this objective, Sílvia Soares, under the guidance of researcher Susana Gomes Guerreiro from the Metabesity group, intends to “develop a nanosystem capable of enhancing the radiosensitivity of prostate cancer cells using gold nanoparticles linked to a miRNA with anti-inflammatory function in order to increase the synergism of the therapy”.

For Sílvia Soares, receiving this grant from the LPCC was “very rewarding” and “gratifying”: “I felt my work was recognized and valued in the scientific environment. In this sense, I intend to take this opportunity to continue my path in science and contribute scientifically to new approaches to radiotherapy in a hospital environment in order to improve the quality of life of patients”.

New personalized therapies for colorectal cancer

The project proposed by Ricella da Silva, which is coordinated by Ipatimup pathologist Fernando Schmitt, aims to analyze the spatial relationships of the components of the tumor microenvironment and the mechanisms underlying the expression of specific biomarkers based on the states of activation or depletion of cells stromal and immune in colorectal cancer. According to Ricella da Silva “the study of biomarkers under spatial observation allows us to identify factors that influence the progression of colorectal cancer, highlight possible molecular targets, and lead to the development of new personalized therapies”.

This approach, adds the researcher, “is extremely relevant for a neoplasm that represents an important global public health problem, due to the increase in incidence and mortality observed in recent decades and the costs associated with diagnosis and treatment”. Colorectal cancer is one of the most common cancers in the world and the incidence in people under the age of 50 has been growing, with the last ten years having doubled from 5 to 10 percent. This LPCC grant, emphasizes Ricella da Silva, “strengthens my enthusiasm and, at the same time, legitimizes and enhances the development of our research work in colorectal cancer”.