H2020Индивидуална стипендия2018–2021

PI3K-VAs · Activation of PI3K signalling in the pathogenesis of Vascular Anomalies

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

Период: 2018-09-01 → 2021-01-11
Финансиране от ЕС: 158 122 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Генетичните мутации, които причиняват разрастване на кръвоносни и лимфни съдове, се изследват чрез механизмите на PI3K сигнализацията. Това помага за по-точна диагноза на пациентите и създаването на инструменти за тестване на нови лекарства за тези редки заболявания.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Activation of PI3K signalling in the pathogenesis of Vascular Anomalies

Vascular malformations are rare diseases that consist in an overgrowth of the blood and lymphatic vessels. These are congenital diseases that are present when the patient is born, thus they occur during embryonic development. Vascular malformations grow with the patient and they are very painful and disfiguring, they cause bleedings, infections and can invade and obstruct vital organs. Recently, we discovered new causing mutations leading to venous malformations, the most common type of vascular malformations. These mutations are similar to those found in epithelial tumours such as breast and colon; however, the specific biology and impact of these mutations in vascular malformations were unknown. Also, the therapeutic effect of targeted therapies that can be repurposed from oncology was underexplored due to the lack of biological insights and preclinical tools for these diseases. With this project we aimed to i) understand the biological mechanisms that lead to the pathogenesis of these diseases, ii) generate state of the art preclinical tools, and iii) assess a spectrum of targeted therapies for these rare diseases. Findings and studies from this project have impacted the way patients with vascular malformations are managed since we have translated our results into the clinic through our clinical partners and this has had an impact on their genetic and molecular diagnosis. Also, our preclinical tools have allowed pharma companies to test molecular inhibitors specifically for these rare diseases, helping in the process towards clinical trials.

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

Цел на проекта

Vascular anomalies are rare soft tissue tumours and malformations formed by abnormal vascular elements of various types, and mainly affect infants, children and young adults. These lesions are painful, many lead to bleeding, infections, organ dysfunction, and they can damage and metastasise to other tissues. Current treatment strategies are invasive, not fully efficient, and there is a high risk of recurrence. To date no specific targeted therapies have been developed. Most of the studies on vascular anomalies are descriptive and focused on their clinical aspects; at the moment, there is a lack of molecular understanding and pre-clinical studies on the field of vascular anomalies. Thus, identifying the causative molecular alterations of vascular anomalies and understanding their biology will lead to more refined diagnoses and will provide better and more directed therapies. Recent published and unpublished observations from our laboratory show that activation of phosphoinositide 3-kinase (PI3K) signalling pathway drive to the developments of a fraction of vascular anomalies; however, the underlying molecular and cellular mechanisms remain enigmatic. In this proposal we aim to (i) unveil alterations in the PI3K signalling pathway components that are involved in the pathogenesis of vascular anomalies, (ii) understand the role of PI3K pathway activation in the development and maintenance of these lesions, and (iii) explore the potential of repurposing PI3K pathway inhibitors for these conditions. For this, we have set up collaboration with clinicians who will provide a large collection of vascular anomalies from patients. Also, in collaboration with Pharma, we aim to use PI3K inhibitors for these diseases. Importantly, these collaborations will allow us to translate our findings into the clinic for future clinical trials. This project proposal seeks to broad our understanding of PI3K activation in vascular biology and to ultimately improve patients’ quality of life.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE · L'Hospitalet De LlobregatКоординаторИспания