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Oncogenic PI3-kinase SIGNED

New biology of oncogenic PI 3-kinase

Total Cost €

EC-Contrib. €

Partnership

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Oncogenic PI3-kinase project word cloud

Explore the words cloud of the Oncogenic PI3-kinase project. It provides you a very rough idea of what is the project "Oncogenic PI3-kinase" about.

nutrient therapies breakthroughs activating functions mutations expertise previously premise oxygen cell lab small pten tissue cells catalytic respectively central class genetically kinase incomplete pharmacological inactivation progression molecule assertion mechanisms innovative endogenous merge sustained mutant encoding predominantly genetic biology contexts activated activation pik3ca unappreciated pi3k uncover mainly hypoxic view death mechanism opposes modulators heterozygous cancer scientific settings understand multiple career signalling subunit alpha tumour mice hypoxia probing host representative regulates drug unbiased oncogenic biased biological ed formulated kill promotor solid gene pi world experimental starved frequently starvation suppressor tumours

Project "Oncogenic PI3-kinase" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITY COLLEGE LONDON Organization address address: GOWER STREET city: LONDON postcode: WC1E 6BT website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	United Kingdom [UK]
Total cost	212˙933 €
EC max contribution	212˙933 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2018
Funding Scheme	MSCA-IF-EF-ST
Starting year	2019
Duration (year-month-day)	from 2019-05-01 to 2021-04-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITY COLLEGE LONDON UNIVERSITY COLLEGE LONDON Organization address address: GOWER STREET city: LONDON postcode: WC1E 6BT website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (LONDON)	coordinator	212˙933.00

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Project objective

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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