A new study by researchers at the Bellvitge Biomedical Research Institute (IDIBELL) has found a cause of multiple resistance in cancer chemotherapy. They discovered that 10% of colon and stomach tumors present wit loss of a molecule called TP53TG1. The functionof TP53TG1 is to prevent activation of YBX1 protein. Without surveillance of TP53TG1 in these gastrointestinal tumors, YBX1 goes to the nucleus of the cell and is responsible for the activation of hundreds of oncogenes that will prevent the death of malignant cells following anti cancer therapy. The The work, published in the Proceedings of the National Academy of Sciences (PNAS) journal has been carried out by the research group of Dr. Manel Esteller, Director of Epigenetics and Cancer Biology Program (PEBC) of IDIBELL, ICREA Researcher and Professor of Genetics at the University of Barcelona.
|Section of a stomach cancer (seen under a microscope) showing aberrant
expression of YBX1 protein (stained brown). Credit:IDIBEL
The introduction of cancer chemotherapy was a revolution for the treatment of this disease in those cases in which the cure is no longer possible only with the mere extirpation of the tumor. Chemotherapy has been shown to be effective in a wide range of patients, but one of its main problems is the emergence of resistance against the anti-tumor drug used. However, it has been known for decades that there are tumors that display cross-resistance against different drugs since its inception, when they have not yet been treated.
The spectrum of resistances induced by this mechanism is extensive and includes drugs commonly used in the treatment of these cancers, such as as 5-fluorouracil, oxyplatinum or irinotecan, but also drugs targeting recent molecular targets such as kinase inhibitors.
Dr. Esteller explains, “we want to study if there is any drug that escapes this mechanism of multiple chemoresistance and also to explore whether returning the activity of the molecule TP53TG1 would mean regaining the sensitivity of these tumors to the drugs analyzed, which would represent a clinical benefit for these patients.”
Citation: Angel Diaz-Lagaresa, Ana B. Crujeirasa, Paula Lopez-Serraa, Marta Solera, Fernando Setiena, Ashish Goyald, Juan Sandovala, Yutaka Hashimotoa, Anna Martinez-Cardúsa, Antonio Gomeza, Holger Heyna, Catia Moutinhoa, Jesús Espadaf, August Vidalh, Maria Paúlesh, Maica Galáni, Núria Salaj, Yoshimitsu Akiyamak, María Martínez-Iniestal, Lourdes Farrél, Alberto Villanueval, Matthias Grossd, Sven Diederichsd, Sonia Guila, and Manel Estellera. “Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer”. Proceedings of the National Academy of Sciences of the United States of America 2016 pp: 201608585
Adapted from press release by IDIBELL – The Bellvitge Biomedical Research Institute.