The main treatment for colon and rectal cancer, chemotherapy, does not work for all patients. An important group, 30%, generates resistance and the tumors cause metastases. They are patients with poor prognoses. Now a team of researchers discovered what triggers this chain of events. In this way, they were able to determine a set of poor prognosis markers and a potential therapeutic target for these patients. The work is published in the journal Nature Communications.
In some cases, and for various reasons, chemotherapy treatment is not enough to eliminate all tumor cells and a part of them survives evolving to an embryonic state. When this happens, the tumor can reappear stronger, being able to resist treatment and generate metastases. Researchers reproduced this process in organoids created from patient cells and verified that cells in this embryonic state express the set of genes, specifically a group of eight genes that are characteristic of these tumor cells and make them more aggressive. Results were confirmed in orthotopic models of colorectal cancer in mice. The IDIBELL and ICO team led by Dr. Alberto Villanueva implanted the organoids in mice, verifying that in vivo the tumor cells continue expressing the eight genes that make them more aggressive. Subsequently, they validated the results in derived PDOX/orthoxenografts of patients.
Possible therapeutic target
The researchers affirm that knowing the factors involved in the embryonic conversion of tumors will make it possible to establish the risk of relapse in patients with colon and rectal cancer.
These discoveries permit estimating the patients’ prognosis and searching for new treatments and personalized approaches for this type of higher-risk patients. Identifying the specific regulator of the embryonic conversion of these cells will make it easier to apply a new way of treating these cases, combining chemotherapy and specific inhibitors of the genes involved. There are already some drugs that can act on tumors with embryonic characteristics.
In addition to Dr. Espinosa and Dr. Anna Bigas, coordinator of the IMIM-Hospital del Mar Research Group on Stem Cells and Cancer and director of CIBERONC, Dr. Toni Celià-Terrassa, coordinator of the Research Group on Cancer stem cells and dynamics of metastasis from the IMIM-Hospital del Mar, and doctors Antonio Barbachano and Alberto Muñoz, from the ‘Alberto Sols’ Biomedical Research Institute (IIBM) and researchers from CIBERONC also participated to the work. Doctors from the Oncology and Pathological Anatomy services of Hospital del Mar participated in the study. The work had the support of the Spanish Association Against Cancer (AECC), of the Fundación hna that supports the group of Dr. Villanueva in the generation of PDOX/orthoxenografts models, and of the National projects of the Carlos III Health Institute.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).