Informace o projektu
ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer
(ALKATRAS)
- Kód projektu
- 675712
- Období řešení
- 9/2015 - 8/2019
- Investor / Programový rámec / typ projektu
-
Evropská unie
- Horizon 2020
- MSCA Marie Skłodowska-Curie Actions (Excellent Science)
- Fakulta / Pracoviště MU
- Středoevropský technologický institut
- Spolupracující organizace
-
University of Cambridge
Anaplastic Lymphoma Kinase (ALK) is an increasingly prevalent oncogene in a number of human malignancies and therefore represents a prominent clinical problem. ALK was first discovered in 1994 when Steve Morris, St. Jude, Memphis, USA cloned this gene from cases of ALCL. Since that time, ALK has been implicated in a number of cancers ranging from neuroblastoma to Non-Small Cell Lung Cancer (NSCLC) and inflammatory myofibroblastic tumours to name a few. In the case of ALCL, ALK is activated as the consequence of a chromosomal translocation whereby the oligomerisation domains of the Nucleophosmin (NPM) gene are juxtaposed to the kinase domain of ALK. The resultant NPM-ALK fusion protein is constitutively active. In the case of NSCLC, an inversion event fuses the Echinoderm microtubule-associated protein-like 4 (EML4) gene to ALK and for neuroblastoma activating point mutations are present, most notably the F1174L ALK mutant. The consistent presence of this oncogene in a number of cancer sub-types suggests not only that common underlying mechanisms of tumorigenesis may exist, but also a unique therapeutic target in ALK. However, as has been the case for a number of kinase inhibitors that have entered the clinical arena, resistance mechanisms have emerged and therefore it is imperative that we pre-empt these activities in order to design better therapeutics. Hence, ERIA was established to discover other ALK-induced processes in order that better therapies can be designed and the ALKATRAS ETN will build on this network to consolidate our collaborations. Our integrated programme will pursue the following objectives: 1) Increase our understanding of the biological mechanisms of ALK-induced tumorigenesis; 2) Develop our understanding of the status and role of the (epi)genome in ALK-induced malignancies; 3) Develop novel therapies and biomarkers; 4) Understand mechanisms of treatment resistance and develop methods to overcome these
Publikace
Počet publikací: 10
2023
-
Patient-derived xenograft models of ALK plus ALCL reveal preclinical promise for therapy with brigatinib
British journal of haematology, rok: 2023, ročník: 20, vydání: 5, DOI
2021
-
STAT3 and TP53 mutations associate with poor prognosis in anaplastic large cell lymphoma
Leukemia, rok: 2021, ročník: 35, vydání: 5, DOI
-
Super-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma
Nature Communications, rok: 2021, ročník: 12, vydání: 1, DOI
2020
-
Analysis mutational landscape in systemic anaplastic large cell lymphoma identifies novel prognostic markers
Rok: 2020, druh: Konferenční abstrakty
-
High activation of STAT5A drives peripheral T-cell lymphoma and leukemia
Haematologica, rok: 2020, ročník: 105, vydání: 2, DOI
-
IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma
Blood, rok: 2020, ročník: 136, vydání: 14, DOI
-
Mutational landscape analysis in systematic anaplastic large cell lymphoma identifies novel prognostic markers.
Rok: 2020, druh: Konferenční abstrakty
2019
-
Analysis of Mutational Landscape in Systemic Anaplastic Large Cell Lymphoma Identifies Novel Prognostic Markers
Rok: 2019, druh: Další prezentace na konferencích
2018
-
Targeted next generation sequencing in anaplastic large cell lymphoma
Rok: 2018, druh: Konferenční abstrakty
-
The Role of Oncogenic Tyrosine Kinase NPM-ALK in Genomic Instability
Cancers, rok: 2018, ročník: 10, vydání: 3, DOI