H2020Индивидуална стипендия2020–2022

PDASwITch · Super-enhancer modules controlling plasticity and response to therapy in pancreatic cancer

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

Период: 2020-09-01 → 2022-08-31
Финансиране от ЕС: 160 932 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Специфични части от ДНК, наречени супер-енхансери, контролират как ракът на панкреаса променя типа си под влияние на околните клетки. Разбирането на тези механизми помага да се разбере защо някои тумори се адаптират и стават устойчиви на терапията.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Super-enhancer modules controlling plasticity and response to therapy in pancreatic cancer

Pancreatic cancer (PaC) is one of the deadliest malignancies worldwide. In last year’s big effort has been made to provide better characterization of this tumour at various layers - mutationally, transcriptionally and epigenetically. The resulting studies have identified individual PDAC subtypes, with the aim to better select treatments for individual patients. However, the subtypes identified represent a snapshot in the tumour evolution and do not provide insights on the dynamics related to the crosstalk between tumour cells and the tumour microenvironment (TME) nor on their interaction with therapy. The ability of tumours to quickly respond to environmental cues leading to reversible changes in the epigenome is likely one major survival adaptation mechanism leading to therapeutic failure. With the PDASwITch project we have generated tools necessary to approach one simple question, in a type of tumour, such as pancreatic cancer with enormous health implication: How and to what extent different cell types in TME - alone or in combination - can modulate the activity of tumour cell super-enhancers to inhibit or promote specific PDAC subtypes? Description of the objectives. In our proposal (PDASwITch), we had set up three different objectives: 1. Establish subtype-specific fluorescent reporter-expressing human PDX cells 2. Generate, phenotype and characterize 3D co-culture models 3. Manipulate subtype switching for clinical application

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

Цел на проекта

Recently discovered subtypes in pancreatic ductal adenocarcinoma (PDAC) have potential to better guide the choice of therapy. However, this is challenged by the lack of robust data, patient heterogeneity, tumour cell plasticity, dynamic crosstalk with surrounding cells, and post-chemotherapy induced alterations. A few transcription factors may act as drivers of specific PDAC subtypes and changes in there expression through aberrant activation of super-enhancers may lead to ‘’subtype switching’’. However, the effect of the tumour-microenvironment on enhancer-driven gene expression programme to promote ‘’subtype switching’’ in pancreatic tumour cells remains largely unexplored. Hence, with this proposal I aim to provide in-depth characterization of this dynamic crosstalk combining reporter tracing through fluorescent labelling of subtype-specific transcriptional drivers of tumour cell states with powerful high throughput single-cell technologies, and super-enhancer single cell profiling which will translate to a clinical study of neoadjuvant chemotherapy with sequential tumour sample profiling. This work will ultimately provide a platform for the development of methods to precisely determine the ""phenotypic"" state of PDAC cells and aid in designing new agents to target these processes, with the ultimate goal of converting non-responder to responder tumours and improve patient outcome.""

Оригинален текст от CORDIS (на английски).

Участници

FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III · MadridКоординаторИспания