A group of Spanish researchers has developed a drug against the CD98hc protein, a new therapeutic target present on the surface of tumor cells, which turns out to be “very powerful and specific for colon cancer tumor cells.”
The research has been directed by the researcher from the Salamanca Biomedical Research Institute (IBSAL), Juan Carlos Montero González, and by the researcher from the Cancer Research Center (joint center of the University of Salamanca and the CSIC), Atanasio Pandiella Alonso , both belonging to the Cancer Cyber. It has also had the participation of Alberto Muñoz Terol’s group, from the Sols-Morreale Biomedical Research Institute (CSIC-UAM), in Madrid, also belonging to Ciberonc.
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, an ADC-type drug was developed that turned out to be very powerful and specific for this type of tumor.
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.
“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,” says Montero.
First, the expression levels of CD98hc in tumor and normal tissue from colon cancer patients 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.
For this purpose, an ADC that specifically recognized CD98hc was developed. Once it penetrates the cell interior, the ADC against the CD98hc protein not only prevents tumor cells from proliferating, but also causes their death, reducing tumor size.
Panidella explains that “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” .
“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,” he adds.
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.
Alberto Muñoz states that, thanks to these studies, they 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 attack more selectively to tumor tissue versus healthy tissue, mitigating side effects.
On the other hand, experts 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.
The study has also been funded by the Carlos III Health Institute, the Ministry of Science and Innovation, the Department of Education of the Government of Castilla y León, and private entities: CRIS Foundation against cancer, Unidos Contra el Cancer of Toro and Province of Zamora (UCCTA), Leonese Association of Women Operated for Breast Cancer (ALMOM) and Ceutí Association of Mastectomized Women (ACMUMA).
