AICAR is the first therapeutic molecule against cancer patented by a Spanish public centre that has reached the clinical trial stage. The drug was developed in 2003 by researchers of the current group of Apoptosis and Cancer at Bellvitge Biomedical Research Institute (IDIBELL) and the Department of Physiological Sciences II, University of Barcelona (UB), led by Joan Gil. In 2004, development rights and exploitation of the product were acquired by the company Advancell, being produced under the trade name of Acadra™.
The drug works by activating mechanisms of programmed death (apoptosis) in tumour cells of chronic lymphocytic leukaemia and other B cell cancers such as mantle cell lymphoma and splenic marginal zone lymphoma.
The drug is capable of acting on the malignant cells without attacking healthy cells. The drugs currently available eliminate healthy T cells (which are part of the immune system that defends the body against infections), along with the tumour, a fact that immunecompromised patients.
So far, the only known molecular target of AICAR was the AMP-activated protein kinase (AMPK). Now, the study published in Blood, coordinated by Joan Gil and which are lead authors the UB-IDIBELL researchers Antonio F. Santidrián and Diana M Gonzalez-Gironès, demonstrates that AICAR induces apoptosis in B lymphocytes by an AMPK independent mechanism. The study shows how AICAR induces apoptosis in cells with mutations in the p53 tumour suppressor gene.
According to the research coordinator, Joan Gil, “this fact means that AICAR could be an interesting therapeutic alternative for patients with chronic lymphocytic leukaemia with altered p53 function and resistance to conventional chemotherapy.”
AICAR has passed pre-clinical studies that evaluated drug toxicity and pharmacodynamics. In 2007 a clinical trial in patients with chronic lymphocytic leukaemia was approved, and it is currently underway. The results of the clinical trial will be published soon.
The research has the cooperation of the Clinical Haematology Service of the Catalan Institute of Oncology and the Hematology Department of the Bellvitge University Hospital. Researchers of the University Hospital Marqués de Valdecilla, Santander-Spain, the Innsbruck Medical University, Austria, the Cochin Institute and the Paris Descartes University, France, have also collaborated.
Santidrián AF*, González-Gironès DM*, Iglesias-Serret D*, Coll-Mulet L*, Cosialls AM*, de Frias M*, Campàs C*, González-Barca E*, Alonso E*, Labi V, Viollet B, Benito A, Pons G*, Villunger A, Gil J*. AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood, 2010 Oct 21;116(16).