A study provides key data for the treatment of cancer with epigenetic inhibitors, 'switches' that activate silenced genes in tumor cells
Scientists from the Biosanitary Research Institute of Granada and the University of Granada reveal critical aspects that will make it possible to optimize the treatment of cancer patients with epigenetic inhibitors
90% of deaths associated with carcinomas are a consequence of the dissemination of cells to other organs of the body, in which they give rise to the formation of secondary tumors or metastases
Their results, published in the prestigious journal Oncogene, will allow the design of more effective and safer personalized therapies with epigenetic inhibitors in cancer patients
A team of scientists from the Granada Biosanitary Research Institute (ibs.GRANADA), the University of Granada (UGR) and the Center for Genomics and Oncology Research (GENYO) has provided important new data to optimize the treatment of cancer patients with inhibitors epigenetic, some 'switches' that reactivate the expression of genes normally silenced in tumor cells.
The researchers, belonging to the group Ae21-Epigenetics in Stem Cells and Cancer from ibs.GRANADA, the Department of Biochemistry and Molecular Biology II of the UGR and the Epigenetics in stem cells and cancer group of GENYO, have studied the role of these epigenetic inhibitors against proteins called Polycomb in carcinomas.
Cancer is one of the leading causes of death worldwide, with almost 10 million deaths annually. 90% of deaths associated with carcinomas are a consequence of the dissemination of cells to other organs of the body, in which they give rise to the formation of secondary tumors or metastases. In order for cancer cells to metastasize, they must be functionally plastic, that is, have the ability to change between different cellular states that allow them to move and colonize new tissues. Therefore, finding effective drugs that inhibit this cellular plasticity is essential to stop the spread of cancer cells and improve the prognosis of cancer patients.
The work, which has been published in the prestigious journal Oncogene, reveals that Polycomb proteins, in addition to regulating the ability of cancer cells to multiply, act as a master regulator of the plasticity necessary to form new tumors during the dissemination phase.
Polycomb proteins are epigenetic regulators against which inhibitors have been developed that are currently being tested in numerous clinical trials as therapy for different types of cancer, including colon, lung and hematological cancers. In this way, the discoveries presented in this article will allow the design of much more effective and safer personalized therapies for cancer patients using these epigenetic inhibitors.
Amador Gallardo, first author of the work, points out that "the new role of Polycomb proteins as guardians of cellular plasticity in cancer cells makes us rethink the role of the epigenome during tumor dissemination."
For its part, David Landeira, Principal investigator of the group and author responsible for this work, points out that "this work reveals a key aspect of the function of the EZH2 protein that will allow a safer application of the inhibitors of said protein in human patients with different types of cancer".
Bibliographic reference:
Gallardo A, Molina A, Asenjo HG, Lopez-Onieva L, Martorell-Marugan J, Espinosa-Martinez M, Griñan-Lison C, Alvarez-Perez JC, Cara FE, Navarro-Marchal SA, Carmona-Saez P, Granados S, Medina P, Marchal JA, Sanchez-Pozo A, Landeira D. EZH2 endorses cell plasticity to non-small cell lung cancer cells facilitating mesenchymal to epithelial transition and tumor colonization. Oncogene (2022). https://doi.org/10.1038/s41388-022-02375-x
Attached images:
Human lung cancer cells expressing the EZH2 protein.