A team of researchers led by the researcher from the Salamanca Biomedical Research Institute (IBSAL) Juan Carlos Montero González and by the researcher from the Cancer Research Center (mixed center of the University of Salamanca and the CSIC) Atanasio Pandiella Alonso, both belonging to the Cyber of Cancer, has developed a “potent and specific” drug for treat colon cancerwhich could also help combat other types of cancer with a high presence of the CD98hc protein.
Their study was based on the previous discovery that colon tumors produce high amounts of an amino acid transporter subunit called CD98hc, a finding that has promoted the development of a modified antibody of the class of ADC (antibody drug conjugate) that specifically attacks colon cancer tumor cells. ADCs are antibodies to which an agent toxic to the cell has been attached. In this way, these drugs add the antitumor effect of the antibody and the antitumor effect of the drug attached to them.
In a previous study, the research team discovered a new therapeutic target on the surface of tumor cells, called CD98hc. Subsequently, against this therapeutic target, a ADC type drug which proved to be very powerful and specific for this type of tumor. “The need to incorporate new drugs aimed at colon cancer led our group to evaluate whether CD98hc could be a good therapeutic target in this type of tumor,” stated Montero.
A drug that causes the death of the tumor cell
First, the expression levels of CD98hc in tumor and healthy tissue from patients with colon cancer were analyzed. In these experiments, it was observed that the amount of CD98hc in colon tumor cells was much higher than in non-tumor (healthy) cells. This difference in expression of CD98hc between the tumor cell and the healthy cell allows preferential action on the tumor cell using, for example, specific antibodies against that protein. With this objective, an ADC was developed that specifically recognized CD98hc and that when it penetrates the cell interior, causes the death of the tumor cell.
“The results obtained with this new drug directed against CD98hc in the different preclinical models of colon cancer open the door for its possible evaluation in clinical trials”
“Due to the clinical effectiveness that this type of drugs are having in other pathologies and the effectiveness that the ADC had against CD98hc, generated by our group in breast cancer, we decided to evaluate the potential of this ADC in colon cancer,” says Pandiella. “In these experiments it was observed – adds Montero – that this ADC had a powerful and specific antitumor activity against colon cancer cells.” The ADC against the CD98hc protein not only prevented the tumor cells from proliferating, but also caused their death, reducing the size of the tumor. The results have been published in Journal of Experimental & Clinical Cancer Research.
Antitumor efficacy of ADC against CD98hc in organoids
These studies were complemented by the work of the Madrid group, which works with organoids, which are experimental models derived from patients. The antitumor efficacy and toxicity of the ADC against CD98hc were evaluated in several organoids generated from colonic normal and tumor tissue from patients with colon cancer.
“In these studies – explains Alberto Muñoz – we were able to verify that the drug directed against the CD98hc protein prevented the growth of tumor organoids and, furthermore, its effect was minimal in healthy organoids. These results indicate that this new drug could more selectively attack tumor tissue compared to healthy tissue, mitigating side effects.”
In short, Pandiella highlights: “The results obtained with this new drug directed against CD98hc in the different preclinical models of colon cancer open the door for its possible evaluation in clinical trials.” On the other hand, it is necessary to mention that the CD98hc protein is also highly expressed in other types of tumors, in addition to colon cancer and breast cancer. Therefore, the use of drugs directed against this target could be useful in other pathologies.