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Twist gain-of-function and loss-of-function cell models




An Italian research group has engineered tumor protein (p53) wild-type cell models for Twist expression control to be used for inhibitors Mouse double minute 2 homolog (MDM2).
They are looking for licence agreement and commercial agreement with technical assistance.



p53 is a tumor suppressor whose inactivation plays a key role in cancer development and drug resistance.
In a large fraction of tumors p53 is inactivated through TP53 gene mutations, but in some tumor types (e.g. sarcomas) p53 is inactivated despite the absence of TP53 gene mutations. In these tumors, the inactivation of p53 is often the result of increased degradation of the p53 protein mediated by the MDM2 ubiquitin ligase.

The research group demonstrated that the overexpression of the protein Twist, detectable in a large fraction of sarcomas but also in a fraction of carcinomas, facilitates the MDM2-mediated degradation of p53 by making p53 more susceptible to MDM2 attack.

The p53:MDM2 interplay is the target of a number of compounds currently under clinical trials. These compounds (MDM2i) are aimed at alleviating p53 from MDM2-mediated degradation and hence at restoring the p53 tumor suppressive activity.
The researchers gathered data indicating that the expression of Twist may significantly impact on the activity of these drugs.

To their knowledge there is no golden standard for this product (another cell model engineered for twist expression) so they can't say that this product is better that another.
There are no information available about preclinical selection of iMDM2 using cell models, but since the data that researchers have for Twist cell models are preliminary, they can't say that
they will work 100% and that they should be used in preclinical phase for the selection of MDM2 inhibitors.
This is why they could say that Standard p53 wild-type cell models need to be engineered for Twist expression.

To perform preclinical evaluation and selection of new iMDM2 on the basis of Twist expression, standard p53 wild-type cell models need to be engineered, while Twist gain-of-function and loss-of-function cell models are ready to use tools.

The industrial liason office of the research center is looking for partners interested in the commercialization of the products such as research tool and/or for drug screening.

Partner expertise sought:

- Specific area of activity of the partner: They are looking for a partner interested in the commercialization of the products as research tool and/or for drug screening.

Advantages & innovations:

Technology advantages: standard p53 wild-type cell models need to be engineered for Twist expression to be used for iMDM2 testing.
Technology applications: the main application is to evaluate activity of p53:MDM2 inhibitors in preclinical phase.
These cell models can be used also as research tools to explore p53 inactivation mechanisms in TP53 wild type tumors, and to study MDM2i resistance mechanisms.

Development Stage:

Field tested/evaluated - 3 different cell lines were consistently characterized; 2 more cell lines are producing promising results; 6 different drugs have already been tested including nutlin3a - AMG 232 - RG7112 - SAR405838; more than 100 cell vitality tests have been performed.


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