Despite intense research efforts, cancer continues to be one of the leading causes of death worldwide. By current estimates, in 2030 close to 22 million new cases will be diagnosed and cancer will cause 13 million deaths worldwide. This is so in spite of the wide toolbox of therapies against cancer assembled over the years. It is thus remarkable that little or no therapeutic use has been made of a whole discipline, heterogeneous catalysis, noted for its specificity and for enabling chemical reactions in otherwise passive environments. At least in part, this could be attributed to practical difficulties: the selective delivery of a catalyst to a tumor and the remote activation of its catalytic function after it has reached its target are highly challenging objectives. Only recently, the necessary tools to overcome these problems seem within reach. CADENCE aimed for a radical development in cancer therapy from a new therapeutic perspective. The central hypothesis is that a growing tumor can be treated as a special type of reactor in which environmental conditions (i.e. the tumor microenvironment, TME) can be catalytically tailored to prevent cancer growth. The catalysts would be used to achieve two objectives: a) depletion of molecules essential to tumor growth and b) generation of toxic products in situ.
To implement this novel approach, CADENCE makes use of core concepts of reactor engineering, as well as of ideas borrowed from bio-orthogonal chemistry and controlled drug delivery. CADENCE has developed a range of catalysts capable to perform one or both of the above described functions, a) and b). These catalysts (as well as other types of therapeutic particles) have been delivered in vitro and in vivo using novel Trojan Horse-based strategies (mainly extracellular vesicles, (EVs), with tumor tropism), achieving delivery efficiencies that were several times higher than those of conventional methods (EPR effect). In addition, some of the catalysts developed were endowed with selective activation capabilities, either remotely (using near-infrared (NIR) light) or through local activation, using molecules overexpressed in the TME, such as glutathione (GSH).
CADENCE ambitions are high, addressing all the key steps from catalyst design to in vivo studies. Its results have provided new perspectives in catalytic therapy for oncology, thanks to the advances obtained along two main avenues, namely: i) catalysts able to simultaneously combine therapies against cancer (e.g. starvation therapy through glucose oxidation along with oxygen generation to avoid hypoxia limitations, or production of reactive oxygen species (ROS), along with the simultaneous depletion of antioxidant molecules); ii) new catalytic vehicles with selective targeting capabilities (the catalytic EVs, developed for the first time in CADENCE are new exciting therapeutic vectors with a wealth of unexplored possibilities). In summary, CADENCE contributes novel elements to the therapeutic toolbox against cancer, opening up possibilities that will certainly continue to be developed in the near future.
