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).
- 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.
Standard p53 wild-type cell models need to be engineered for Twist expression to be used for iMDM2 testing.
The main limitation is that these models are designed for screening purposes therefore they can not reflect actual single patient response.
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.