TECHNOLOGY DESCRIPTION
Twist GAIN-of-function and LOSS-of-function cell models were developed and used for preclinical p53:MDM2 inhibitors evaluation, preliminary demonstrating that the expression of Twist hampers their efficacy.
These findings support patient stratification on the basis of twist expression for treatment of a large fraction of sarcomas but also of a fraction of carcinomas. (Piccinin et al., Cancer Cell, 22, 404-415, Sept 11 2012).
Developmental stage:
- 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.
BENEFITS
Standard p53 wild-type cell models need to be engineered for Twist expression to be used for iMDM2 testing.
LIMITATIONS
The main limitation is that these models are designed for screening purposes therefore they can not reflect actual single patient response.
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.
MATERIALS
Readiness Level (TRL)
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STATUS
Current status
Currently the knowhow related to the technology is secret. The best IPR protection strategy is under evaluation.
AVAILABILITY
Available for
Licensing
INVENTOR / TEAM
Roberta Maestro, Sara Piccinin
