Εvaluation of new quinazolines derivatives as radiosensitisers and anticancer agents in cancer cell lines that over express receptors of the ErbB family

Quinazolines are anticancer agents that are clinically used for the targeted treatment of tumors where the ErbB receptors are overexpressed or bear specific mutations. These agents can also act as radiosensitizers. The purpose of this Ph.D. project is the evaluation of new anticancer quinazolines derivatives as radiosensitizers. These will belong to the following categories:

1. Derivatives that inhibit the tyrosine kinase domain and have inhibitory action in specific mutations of EGFR: deletions of exon 19 (del 746-750) or/and the exon 21 (L858R) (1^st generation)
2. Derivatives that have broader activity to overcome EGFR resistant mutations to the 1^st generation and inhibit all ErbB family signaling (2^nd generation).
3. Derivatives that have high specificity for the T790 mutation of EGFR, which is the most common mechanism of resistance to the therapy using the first two generation quinazolines (3^rd generation).

For the purpose of this study, the new produced quinazolines derivatives are evaluated for their anti-cancer activity and for their ability of radiosensitizing. The most promising radiosensitizers of this study will be compared with the current quinazolines that are used nowadays in clinical routine. The ultimate goal is to propose new promising anticancer agents that can also act as radiosensitizers.