H2020Индивидуална стипендия2019–2021

Gal3-BrainMets · A novel immunotherapy against brain metastasis: Anti-Galectin-3

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-02-01 → 2021-01-31
Финансиране от ЕС: 170 122 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Ролята на протеина галектин-3 при метастазите на рак на гърдата в мозъка се анализира чрез влиянието му върху имунните клетки. Разбирането на този механизъм може да помогне за разработването на нова имунотерапия при заболявания с лоша прогноза.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

A novel immunotherapy against brain metastasis: Anti-Galectin-3

Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. The treatments for this disease are improving patients’ life expectancy. Unfortunately, the increase of free-disease survival also comes with a higher probability for suffering from the dissemination of the cancer cells to distant organs (metastasis). Amongst all the potential sites that circulating tumour cells may colonise, the central nervous system has the worst prognosis: 1 month without treatment or ca. 14 months even after the most advanced therapies. Harnessing the body's immune response to tumours (immunotherapy) has recently shown promise for the treatment of primary cancers outside the brain. Together with surgery, radiation and chemotherapy, it has become the fourth pillar for the treatment of a broad panel of cancer types. Although this strategy has gained great momentum in the clinic, only a few studies have tested its validity for breast cancer brain metastasis. The neuroinflammatory scenario driven by the immune system during the brain colonisation of tumour cells is a hallmark. One key molecule in the immunogenic response within the brain is β-galactoside-specific animal lectin galectin-3 (Gal-3). Galectin-3 is a promiscuous protein of the lectin family expressed both in cancer cells and a variety of immune system cell types (microglia included), constitutively or in response to different kinds of insults. In other diseases within the central nervous system, microglial Galectin-3 has shown a negative effect on disease progression (e.g. Alzheimer’s and Parkinson’s’ disease) turning microglia into a harmful phenotype. Since microglial cells are the resident macrophages in the brain, it is of vital importance to study the role that this protein may exert on microglial activation during brain metastasis progression. This project seeks to find new strategies to shift the microglial response into an anti-metastatic state, and thus, improve survival in breast cancer brain metastasis (BCBM) patients, an urgent and unmet clinical need. Our approach will use a balanced combination of established and novel in vitro and in vivo brain metastasis models, in which anti-tumourigenic therapies that have not previously been considered in a BCBM context will be tested.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The development of new cancer treatments has significantly improved life expectancy of patients. However, these advances increase the risk of suffering from secondary tumours (metastases). Particularly, breast cancer brain metastases are a major cause of morbidity, with meagre life expectancy (3-18 months). These facts highlight the urgent need to find better treatment against this disease.Immunotherapy has recently gained great momentum in the clinic to treat different type of cancers. However, its therapeutic use for metastatic spread to the central nervous system (CNS) remains scarce. The immune response within the CNS during metastasis progression greatly depends on microglial cells (resident CNS macrophages). Their roles in neuroinflammatory and neurodegenerative processes have been intensely investigated, whereas their function in metastasis has received minor attention. During brain metastasis, microglia show impaired immune defence, secreting a variety of anti-inflammatory cytokines (e.g. IL-10 and TGF-B) and growth factors which may contribute to metastasis progression.A key molecule which might alter such adverse behaviour is beta-galactoside-specific animal lectin galectin-3 (Gal-3). Studies of this promiscuous protein has shown a pivotal role during tumour progression and metastasis to non-CNS sites. Importantly, recent studies from Prof Venero’s group have shown how inhibition of microglial Gal-3 shifted the phenotype of these cells into a more pro-inflammatory state. Therefore, since pro-inflammatory state in microglial cells has been described to exert anti-metastatic effects, Gal-3 inhibition may provide a powerful and novel brain metastasis immunotherapeutic approach. Moreover, the fact of the existence of Gal-3 drugs in current clinical trials enhance the possibility of using this strategy as neo-adjuvant therapy to treat breast cancer patients at risk of brain metastasis.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSIDAD DE SEVILLA · SevillaКоординаторИспания