A study points to new therapeutic targets for tumors associated with chronic inflammation

July 11, 2018

Scientists headed by ICREA researcher Angel R. Nebreda at the Institute for Research in Biomedicine (IRB Barcelona) report a new mechanism that contributes to the development of inflammation-associated colon cancer and points to new therapeutic targets. The study has been published in the journal EMBO Molecular Medicine.

More than a million people worldwide are diagnosed with colon cancer every year. Although many of these cases are spontaneous, chronic inflammation is one of the main causes underlying the development of this disease.

"Our study demonstrates that the capacity of myeloid cells to enhance tumorigenesis is determined by the protein p38. In particular, we have identified an important contribution of the hormone IGF-1, which is activated by p38 in myeloid cells", explains Nebreda, head of the Cell Sigalling and Cell Cycle lab.

The research has been done using models of acute and chronic inflammation in genetically modified mice or in mice treated with pharmacological inhibitors.

IGF-1 and inflammation

IGF-1, a hormone similar to insulin, emerges as a potential therapeutic target-- preferably in combination with prior detection of inflammatory infiltration in biopsies of patients and levels of IGF-1--in intestinal diseases associated with inflammation. This finding could help to address the low success rate achieved by pharmacological inhibitors of p38 in clinical trials in patients with intestinal inflammatory disease who are predisposed to colon cancer.

"We found that p38 inhibition specifically in myeloid cells protects mice against inflammation-associated colon cancer, and this protective effect is associated with a reduced production of chemokines, which are crucial for the recruitment of cells from the immune system", explains Catrin Youssif, first author of the study and current alumnus of IRB Barcelona.

The study demonstrates that the genetic or pharmacological inhibition of IGF-1 suppresses the recruitment of inflammatory cells and reduces the burden of colon cancer tumours associated with inflammation.

"On the basis of our findings, we propose that decisions regarding therapy should take into consideration the inflammatory conditions and the levels of IGF-1 in biopsies of patients with inflammatory intestinal diseases or colitis-associated cancer," conclude the authors of the study.
-end-
In addition to funding from the European Research Council (ERC), the study has been supported by the "Fundació La Marató", the Ministry of Economy and Competitiveness of Spain, and the "Agencia de Gestión de Ayudas Universitarias y de Investigación (AGAUR)" run by the Catalan Government.

The study has been done in collaboration with researchers at CNIO and Hospital Ramón y Cajal in Madrid, and has involved IRB Barcelona's Histopathology Facility and Biostatistics and Bioinformatics Facility, as well as Jaume Comas and Teresa Rodrigo Calduch, from the University of Barcelona.

Reference article:

Catrin Youssif, Monica Cubillos-Rojas, Mònica Comalada, Elisabeth Llonch, Cristian Perna, Nabil Djouder, Angel R Nebreda

Myeloid p38α signaling promotes intestinal IGF?1 production and inflammation?associated tumorigenesis

EMBO Molecular Medicine (2018): doi: 10.15252/emmm.201708403

Institute for Research in Biomedicine (IRB Barcelona)

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.