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Oncogenic PI3-kinase

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New biology of oncogenic PI 3 kinase

PI 3-kinase (PI3K) signalling regulates multiple cell functions and is one of the most frequently genetically-activated pathways in cancer. This is mainly due to activating mutations in PIK3CA (the gene encoding the PI3Kα catalyti... ver más

30/04/2021

UNIVERSITY COLLEGE...

213K€

Presupuesto del proyecto: 213K€

Líder del proyecto

UNIVERSITY COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-04-30

MSCA-IF-2018: Individual Fellowships

I+D

Cerrada hace 6 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UNIVERSITY COLLEGE LONDON

212.93K€ | Lider

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Duración del proyecto: 25 meses Fecha Inicio: 2019-03-19
Fecha Fin: 2021-04-30

Líder del proyecto

UNIVERSITY COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 213K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto PI 3-kinase (PI3K) signalling regulates multiple cell functions and is one of the most frequently genetically-activated pathways in cancer. This is mainly due to activating mutations in PIK3CA (the gene encoding the PI3Kα catalytic subunit) or inactivation of the tumour-suppressor PTEN (which opposes PI3K signalling). Solid tumours are most often hypoxic and nutrient-starved. The central premise of my proposal is that PI3K signalling has thus far been predominantly investigated under experimental settings not representative of these cancer-relevant tissue contexts. In our view, this has resulted in an incomplete understanding of PI3K biology in cancer. Based on this assertion, I have formulated two key objectives: (1) To uncover previously-unappreciated signalling mechanisms of oncogenic PIK3CA under cancer-relevant conditions of long-term starvation and/or hypoxia. (2) To understand the mechanism of cell death induced by an innovative, new type of PI3K modulators, generated by the Host Lab, that kill PIK3CA-mutant cancer cells under hypoxic conditions. These objectives will be achieved by, respectively: (1) Biased and unbiased genetic and pharmacological approaches in cells and mice, including probing signalling under conditions of (A) nutrient and/or oxygen starvation (B) sustained low-level signalling due to genetic PIK3CA activation in the heterozygous state and from the endogenous promotor, as is the case in cancer. (2) Using unique small-molecule PI3K pathway modulators developed in the Host Lab, in cell-biological and signalling studies. These objectives will merge my expertise in signalling under nutrient-starved conditions with world-class know-how in PI3K cancer studies and drug development in the Host Lab. This proposal aims to make scientific breakthroughs in understanding cancer-related PI3K signalling, promoting the progression of my career and allowing the Host Lab to achieve its key long-term aim to make PI3K-based cancer therapies work.

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