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FP6

TRKCANCER — Result In Brief

Project ID: 37758
Funded under: FP6-LIFESCIHEALTH
Country: France

Inducing selective killing of metastatic cancer

Cancer metastasis hampers effective treatment and disease eradication. A European consortium addressed this issue by targeting TrKB. This neurotrophic tyrosine kinase receptor suppresses programmed cell death, apoptosis, in cancer cells.
Inducing selective killing of metastatic cancer
Understanding the mechanisms of cancer establishment and metastasis is of prime importance for designing effective therapeutic regimes. Resistance to anoikis – a form of apoptosis that occurs when cells lose their interaction with the extracellular matrix – has been suggested as a potential cancer cell survival mechanism during metastases formation.

Previous research showed that TrKB can induce cells to aggregate and form tumours and metastases in vivo, indicating that TrKB is a potent suppressor of anoikis. The EU-funded project ‘The anoikis suppressor TrKB as a target for novel anti-cancer agents’ (TRKCANCER) aimed to validate TrKB as a target for anti-cancer drugs. The ultimate goal was to restore anoikis and cause circulating and metastatic cells to die.

Project partners developed in vitro cell-based systems for abrogating TrKB-mediated signalling. Additionally, new mouse models for metastasis were developed which helped scientists identify potential biomarkers of the TrKB pathway. Novel and potent small molecule inhibitors were designed and tested in vitro with the aim to generate anti-cancer drugs. Three of these inhibitors were selected for in vivo evaluation of anti-metastatic properties.

Although further work is required for the TRKCANCER project deliverables to be commercially exploited, the results of research into TrKB as an anti-cancer target are encouraging. This suggests that restoration of the apoptotic mechanism in cancer is a valid therapeutic approach.

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