A new line of cancer research based on some of the active principles contained in broccoli was presented by the Italian company, Indena during the 95th World Congress on Cancer Research in Orlando. The Congress, organized by the American Association on Cancer Research (AACR), is one of the sector's most important gatherings and attracts an attendance of over 15,000 scientists including oncologists, epidemiologists and researchers from all over the world.
Exploration of these molecules, known as isothiocyanates, is parallel to Indena's oncological research into new taxanes, the topic of three other studies presented at Orlando. The Italian company, a leading player in research and the production of active principles and extracts derived from plants, aims to identify new and promising molecules of vegetable origin. These can then be developed by the pharmaceutical industry to produce innovative cancer treatment, which is less invasive as well as less subject to pharmacological resistance.
The new line of research focuses on the specific active principles extracted from broccoli and other vegetables in the Brassica family. Only recently however it has been discovered that certain molecules contained in broccoli, the isiothiocyanates deriving from the enzymatic transformation of glucosinolates, directly inhibit cell growth, inducing the phenomena of programmed cell death (apoptosis). Moreover, exploiting the capacity of the isiothiocyanates to stimulate cells in the production and activation of the detoxifying enzymes, studies have been made to explore the possibility that this mechanism is able to contrast the insurgence of pharmacological resistance, especially in the case of chemotherapy using cisplatin.
Indena's pre-clinical research has shown that the use of glucosinolates/isiothiocyanates could offer a considerable therapeutic advantage in overcoming resistance to radio and chemo therapy. This study was carried out in conjunction with the Bologna Research Institute for Industrial Crops and Rome's Catholic University of the Sacred Heart.
During the AACR Congress, more detailed research findings were presented to illustrate IDN 5390, an innovative taxane derivative, previously selected by Indena in the chain of new taxanes. This drug's capacity was thus shown to induce an inhibition of motility in endothelial cells in non-cytotoxic concentrations. This property, combined with its oral bioavailability and high tolerance levels, allows daily treatment to be maintained over a long period. The study presented at Orlando was conducted together with the Roswell Park Cancer Institute in Buffalo (NY).
The other line of research in which Indena is involved and which was presented at the AACR, follows the route of ortataxel, an analogue of active paclitaxel taken orally and less subject to resistance. This derivate of 14-hydroxy-baccatin, at present in clinical phase II, is quite promising and it has stimulated a search for new analogues with better chemical-physical features and anti-tumour action. A series of synthetic molecules, object of this study, has shown interesting potential on breast tumours.
This study was carried out in collaboration with the Roswell Park Cancer Institute in Buffalo (NY), the Institute of Organic Chemistry and Fotoreactivity (ISOF) of the CNR in Bologna and the A. Marchesini Institute of Organic Chemistry in Milan.
Clinical results were presented with regard to patients with ovarian cancer. It has been shown that there is an increase in the beta tubulin isotype III (TUBB4) in tumours that resist paclitaxel therapy. Beta tubulin is the classical target of this class of compounds. Since TUBB4 expression is low in non-tumoral ovarian tissue, it could be an important target in developing new anti-tumoral agents that can overcome taxane resistance. This study was carried out at the Gemelli Hospital in Rome and the Catholic University of the Sacred Heart in Campobasso.