Nav: Home

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:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

The Emperor of All Maladies: A Biography of Cancer
by Siddhartha Mukherjee (Author)

The Cancer-Fighting Kitchen, Second Edition: Nourishing, Big-Flavor Recipes for Cancer Treatment and Recovery
by Rebecca Katz (Author), Mat Edelson (Author)

The Truth about Cancer: What You Need to Know about Cancer's History, Treatment, and Prevention
by Ty M. Bollinger (Author)

F*ck Cancer: A totally inappropriate self-affirming adult coloring book (Totally Inappropriate Series) (Volume 4)
by Jen Meyers (Author)

Chris Beat Cancer: A Comprehensive Plan for Healing Naturally
by Chris Wark (Author)

Anticancer: A New Way of Life
by David Servan-Schreiber MD PhD (Author)

Keto for Cancer: Ketogenic Metabolic Therapy as a Targeted Nutritional Strategy
by Miriam Kalamian EdM MS CNS (Author), Thomas N. Seyfried (Foreword)

AJCC Cancer Staging Manual
by Mahul B. Amin (Editor), Stephen B. Edge (Editor), Frederick L. Greene (Editor), David R. Byrd (Editor), Robert K. Brookland (Editor), Mary Kay Washington (Editor), Jeffrey E. Gershenwald (Editor), Carolyn C. Compton (Editor), Kenneth R. Hess (Editor), Daniel C. Sullivan (Editor), J. Milburn Jessup (Editor), James D. Brierley (Editor), Lauri E. Gaspar (Editor), Richard L. Schilsky (Editor), Charles M. Balch (Editor), David P. Winchester (Editor), Elliot A. Asare (Editor), Martin Madera (Editor), Donna M. Gress (Editor), Laura R. Meyer (Editor)

Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer
by Thomas Seyfried (Author)

The Metabolic Approach to Cancer: Integrating Deep Nutrition, the Ketogenic Diet, and Nontoxic Bio-Individualized Therapies
by Dr. Nasha Winters ND FABNO L.Ac Dipl.OM (Author), Jess Higgins Kelley MNT (Author), Kelly Turner (Foreword)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Circular
We're told if the economy is growing, and if we keep producing, that's a good thing. But at what cost? This hour, TED speakers explore circular systems that regenerate and re-use what we already have. Guests include economist Kate Raworth, environmental activist Tristram Stuart, landscape architect Kate Orff, entrepreneur David Katz, and graphic designer Jessi Arrington.
Now Playing: Science for the People

#503 Postpartum Blues (Rebroadcast)
When a woman gives birth, it seems like everyone wants to know how the baby is doing. What does it weigh? Is it breathing right? Did it cry? But it turns out that, in the United States, we're not doing to great at asking how the mom, who just pushed something the size of a pot roast out of something the size of a Cheerio, is doing. This week we talk to anthropologist Kate Clancy about her postpartum experience and how it is becoming distressingly common, and we speak with Julie Wiebe about prolapse, what it is and how it's...