Dr. Alberto Muñoz's team has collaborated in a relevant study led by Dr. Atanasio Pandiella of the Centro de Investigación del Cáncer de Salamanca in which a new therapeutic target for colon cancer is described.
It is a conjugated antibody directed against a protein that is mainly expressed on the surface of tumour cells in colon cancer.
This important study has been led by Juan Carlos Montero González, from the Institute of Biomedical Research of Salamanca (IBSAL) and Dr. Atanasio Pandiella Alonso, from the Cancer Research Centre (a joint centre of the CSIC and the University of Salamanca), both belonging to the Cancer CIBER, together with researchers from the group "Colon cancer: Organoids, microenvironment and vitamin D" group of the Cancer Department of the Sols-Morreale Biomedical Research Institute (CSIC-UAM), led by Dr. Alberto Muñoz Terol.
Colorectal cancer is the most common neoplasm in Spain: more than 42,000 new cases are diagnosed each year. Worldwide, it is also one of the cancers with the highest incidence and mortality rates. Despite therapeutic advances in recent decades, colorectal cancer remains an incurable disease when it is not diagnosed in its early stages.
The work now published builds on a previous discovery about colon cancer tumour cells. These cells were found to express high amounts of a subunit of an amino acid transporter protein called CD98hc on their surface. To find out whether healthy colon cells and healthy cells adjacent to the tumour also expressed this protein, the authors of this study performed genomic and proteomic analyses and observed that CD98hc is significantly more abundant in tumour cells than in adjacent healthy cells from biopsies of colon cancer patients.
This finding prompted the development of a specific antibody against CD98hc. This antibody had a special feature: the researchers had modified it by conjugating a cytotoxic agent to it. Thus, once the antibody recognises the target on the tumour cell and is internalised by the tumour cell, the toxic agent is released, killing the cell. Antibodies that carry a cytotoxic compound are called ADCs (antibody drug-conjugates) and are currently being used in some tumours, such as triple-negative breast cancer.
Subsequently, the authors of this work carried out in vitro studies and demonstrated that the antibody designed against the CD98hc protein had potent and specific anti-tumour activity against colon cancer cells. The antibody not only prevented tumour cells from proliferating, but also caused their death, thereby reducing tumour size. The researchers therefore claimed to have discovered a new drug with a possible dual anti-tumour effect: that of the antibody and that of the toxic agent attached to it.
This work recently published in the Journal Experimental Clinical Cancer Research was complemented by studies conducted by Dr. Antonio Barbáchano, Dr. Asunción Fernández-Barral and Dr. Alberto Muñoz (at the IIBM) on organoids, which are three-dimensional cellular models derived from patient tissues. The researchers evaluated the anti-tumour efficacy and toxicity of the antibody against the CD98hc protein in organoids generated from both normal and tumour tissue from colon cancer patients. In these studies," explains Dr Muñoz, "we were able to verify that the drug directed against the CD98hc protein prevented the growth of tumour organoids and, moreover, its effect was minimal in healthy organoids. These results indicated that this new drug could target tumour tissue with a certain selectivity towards healthy tissue, which could mean that side effects would be limited.
The results obtained with this modified antibody in different preclinical models of colon cancer," adds Dr. Atanasio Pandiella, "open the door to its possible evaluation in clinical trials. This research represents a ray of hope for current and future colon cancer patients.