**6. Conclusions**

In conclusion, ricin is a highly cytotoxic plant protein and has been of grea<sup>t</sup> utility to develop a number of anti-cancer immunotoxins. Ricin, and of some other RIPs, are able to act on multiple molecular targets inside the cell, thus triggering di fferent death pathways; this makes such proteins more attractive for cancer treatment than conventional chemotherapy, in which one of the major problems is the rise of resistant cells [67,125]. However, ricin-containing ITs have also been shown to exhibit many limitations, such as unspecific toxicity, organ toxicity (mainly liver, kidney, and vasculature), immunogenicity, fast removal from blood stream, and lysosomal degradation inside cells. As a result, despite of the significant e fforts made over the past few years, ricin as therapeutic agen<sup>t</sup> has not achieved much impact at the clinical level. The challenge is still open, and frontline research is directed towards recombinant immunotoxins and nanocarriers, or towards other novel techniques such as the vector-driven expression of active plant toxin genes in tumor cells [109,126].

Although ricin is not toxic enough to hypothesize a use over a wide area for terrorist purposes, the availability of castor beans and the quite simple procedure for rough ricin purification have stimulated the interest of criminals and terrorists for small-scale biocrimes. This justifies researchers' efforts to obtain faster and more sensitive ricin detection tests. Furthermore, the study of inhibiting or neutralizing molecules and the timing of clinical events following ricin intoxication could lead to the definition of one or more validated therapies.

Finally, the use of castor bean derivatives should be carefully monitored because of the potential presence of active ricin. In fact, the large use of these products in agriculture, without an e ffective ricin inactivation, has already caused several cases of animal intoxication, and can be hazardous for human health.

**Funding:** This work was supported by funds for selected research topics of Alma Mater Studiorum—University of Bologna and by the Pallotti Legacies for Cancer Research.

**Conflicts of Interest:** The authors declare no conflict of interest.
