Final Report Summary - APOTHERAPY (CD40 ligand-based modalities for the treatment of solid tumours)
The APOTHERAPY project brought together expertise from academic and biotechnology sectors across seven European countries with the aim of developing and validating novel anti-cancer agents with a wide therapeutic index and minimal side-effects. The focal point of the research was the utilisation of combined approaches which attack the tumour cell at multiple levels, achieving maximal apoptosis while limiting the risk of drug resistance. These approaches involve the efficient delivery of a pro-apoptotic molecule to cancer cells in combination with inhibitors of anti-apoptotic signal transduction pathways.
Apoptosis induced by CD 40 engagement is traumatically augmented in the presence of inhibitors of the phosphoinositide 3-kinase /akt pathway which is frequently found activated in human tumours. Through the APOTHERAPY project, novel PI3 kinase antagonists have been developed and evaluated for their in vitro and in vivo capacity to kill tumour cells and amplify the CD40L mediated effects on carcinoma cell growth and metastasis. Of particular interest is the development of a new PDK1 specific inhibitor, the first of its kind, that was demonstrated to confer significant anti-tumour effects.
The APOTHERAPY project has thus developed and evaluated novel anti-cancer strategies which will be directly applicable to the clinic for the benefit of cancer sufferers. Thus, the project has led to small-scale clinical studies in patients with bladder cancer which have demonstrated the feasibility and validity of the APOTHERAPY concept and paved the way for future phase 1 clinical trials.
Apoptosis induced by CD 40 engagement is traumatically augmented in the presence of inhibitors of the phosphoinositide 3-kinase /akt pathway which is frequently found activated in human tumours. Through the APOTHERAPY project, novel PI3 kinase antagonists have been developed and evaluated for their in vitro and in vivo capacity to kill tumour cells and amplify the CD40L mediated effects on carcinoma cell growth and metastasis. Of particular interest is the development of a new PDK1 specific inhibitor, the first of its kind, that was demonstrated to confer significant anti-tumour effects.
The APOTHERAPY project has thus developed and evaluated novel anti-cancer strategies which will be directly applicable to the clinic for the benefit of cancer sufferers. Thus, the project has led to small-scale clinical studies in patients with bladder cancer which have demonstrated the feasibility and validity of the APOTHERAPY concept and paved the way for future phase 1 clinical trials.
