CENTRO DI RIFERIMENTO ONCOLOGICO
Technology Transfer Opportunities Contact: Ermes Mestroni emestroni@cro.it
ACTION OF RETINOIC ACID ON CANCER CELLS ELUCIDATED Technology Overview The Cancer Bio-Immunotherapy Unit of CRO Aviano has investigated the action of retinoic acid (RA). Its impact on cancer cells when combined with other cellular and chemical agents was also observed. Trials have shown that retinoids exhibit both preventive and therapeutic action for certain cancers. Aiming to extend on this potential, a European funded project researched the anti-cancer action of retinoic acid and the possibility of combination therapy with other drugs. Dexamethasone and hydrocortisone are steroid hormones which can be used as part of therapy. Dexamethasone is given to patients undergoing chemotherapy to counteract certain side effects of the treatment and can be used as an anti-cancer drug in its own right. CRO researchers investigated the effects of these two glucocorticoids on Mantle cell lymphoma cells: numbers of MCL cells were not significantly increased by physiological concentrations of either steroid. Previous trials had implicated the steroids as promoting increased numbers of Epstein Barr virus immortalised B lymphocytes. The team also focused on the TRAIL (Tumour necrosis factor alpha-related apoptosis-inducing ligand) death signalling pathway. The isomer 9-cis-RA was able to sensitise MCL cells to TRAIL dependent apoptosis but without the involvement of TRAIL receptors. Moreover, 9-cis-RNA inhibits the growth promoting effect in MCL cells activated by CD40 (cluster of differentiation 40) cells with or without interleukin-4.
Advantages √ possibilities for the use of RA isomers both in combination therapy for cancer and exploitation of cross-talk between significant pathways involved; √ beneficial antiprolific properties of RA in MCL cells, not affected by either dexamethasone or hydrocortisone; √ apoptosis through death receptor signalling: RA ability to inhibit basal growth of MCL cells as well as antagonising stimulation of their proliferation by external factors such as CD40.
Development Stage Specific R&D activities successfully implemented and significant results obtained within the framework of EU funded programmes (e.g. ANTICANCER RETINOIDS project).
Looking for ⇒ collaborations for further research or development support.
More Information Dr. Riccardo Dolcetti, Head Cancer Bio-Immunotherapy Unit rdolcetti@cro.it +39-0434-659-660/676