RoNDBioCan · NLRP3 in cancer: Deciphering the role of NLRP3 in the DNA Damage response pathway
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2018-01-01 → 2020-04-21
- Финансиране от ЕС
- 173 076 €
- Участници
- 2
- Схема
- MSCA-IF-EF-RI
Линиите свързват координатора с партньорите.
Накратко на български
Имунният фактор NLRP3 и неговата роля при възстановяването на увредената ДНК в клетките на белия дроб се анализират в този проект. Разбирането на тези процеси помага за откриването на нови механизми за развитие на рака и по-добри методи за диагностика.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
NLRP3 in cancer: Deciphering the role of NLRP3 in the DNA Damage response pathway
The identification of new therapeutic strategies in the treatment of lung cancer is a research priority. Today 40% of these cancers remain of undetermined origin, so there is a crucial need to identify new mechanisms behind lung cancer. The action of current therapies relies mainly on the induction of highly toxic DNA lesions, where side-effects themselves lead to considerable morbidity and mortality. The MSCA project RoNDBioCan “Deciphering the Role of NLRP3 in the DNA Damage Response (DDR) pathway and evaluation of the potential predictive role of NLRP3 as a Biomarker in the treatment of lung Cancer” aims at understanding the molecular processes driving lung cancer. Tumors cells causes inflammation within a tissue. If the main role of inflammation is to participate in the elimination of tumors, multiple studies show that it also promotes their development. In our lab, we study an immune factor called NLRP3 involved in a protein complex called NLRP3 inflammasome. The aim of this complex is to secrete inflammatory cytokines involved in the immune response. Evidence has shown that NLRP3 is deregulated in a wide range of disorders, and its expression is systematically absent in lung cancer cells. Interestingly, our research group showed that NLRP3 is also an important factor for the response to DNA damage. Poor repair of these alterations could have insidious effects by causing the appearance of mutations, thus promoting the process of carcinogenesis. It is therefore crucial to better understand how the different functions of NLRP3 are regulated. The objectives of this Marie Sklodowska Curie Action (MSCA) were to (1) decipher the molecular mechanism of NLRP3 function in the DDR pathway in non-tumoral and tumoral lung epithelial cells and to (2) evaluate the predictive role of NLRP3 expression in response to chemotherapy in the treatment of lung cancer. Another objective of the MSCA individual fellowship was to promote the development of the individual researcher and to sensitize a broad public to MSCA. At the scientific level, RoNDBioCan contributed significantly to european excellence and society in that it has strengthen the knowledge of lung tumorigenesis and helped the career development of the fellow.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Cancer represents one of the main causes of death in the European Union (WHO). Particularly, non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is the leading cause of cancer-related death worldwide. Despite significant therapeutic improvements, the survival rate of patients with advanced stage NSCLC remains dismal, signifying a critical need to elucidate the molecular processes driving NSCLC. Inflammasomes are major drivers of inflammatory responses and are deregulated in a wide range of disorders, yet their participation in carcinogenesis is largely unknown. Genome analyses reported that the NLRP3 receptor, component of the NLRP3 inflammasome, is affected by somatic alterations in 20% of NSCLC. Moreover, recent evidence has shown that NLRP3 is essential for the activation of the ATM/CHK2 pathway in response to double strand breaks (DSBs), while its expression is systematically absent in NSCLC cells. Based on these data, we hypothesize that NLRP3 is a key factor in the DDR pathway to DSBs and in the maintenance of genome integrity in lung epithelial cells, and as a consequence may play a key tumor suppressor role. The objectives of RoNDBioCan will be to decipher the molecular mechanism of NLRP3 function in the DDR pathway and to evaluate the therapeutic potential associated with NLRP3 expression. By characterizing novel NLRP3 partners and examining the impact of NLRP3 re-expression on tumor development in vivo, RoNDBioCan will significantly improve the current knowledge regarding NLRP3 participation in lung cancer. Given that the poor outcome associated with NSCLC is mostly due to limited curative options, there is an urgent need to identify new biomarkers and additional treatments to reduce the current burden of lung cancer. This work will thus considerably contribute to the development of new effective and personalized therapeutic approaches to help improve the prognosis of lung cancer patients.
Оригинален текст от CORDIS (на английски).
Участници
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Данни: CORDIS, © Европейски съюз