Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Double trouble: A drug for alcoholism can also treat cancer by targeting macrophages

30.01.2020

New research presents a first-of-its-kind cancer treatment strategy that targets a pro-tumor protein FROUNT and suppresses tumor-associated macrophages

Developing a therapy to combat cancer remains one of the most difficult challenges in medical research. Cancer owes its notorious identity to the fact that the cancer cells use the host's own immune system to grow and spread, ultimately becoming deadly.


An anti-alcoholism drug--disulfiram, it may be possible to disrupt tumor progression.

Credit: Tokyo University of Science

Immune cells like macrophages, which ordinarily fight to protect normal cells, are hijacked by malignant cancer cells, and populate the environment around the tumors, becoming tumor-associated macrophages (TAMs).

In fact, it was found that the cancerous tissue of patients for whom immunotherapy was not successful was indeed rich in macrophages, confirming the link between the cancer and the TAMs.

It is these TAMs that produce signaling proteins like chemokines and trigger the inhibitory immune checkpoint releases that create an immunosuppressive tumor environment, which protects the cancer cells and allows their accelerated growth. Since it is the TAMs that facilitate the spreading of cancer cells, regulating them as a therapeutic strategy for combating cancer has gained attention in recent years.

A research group led by Yuya Terashima from the Tokyo University of Science saw this as an opportunity to explore the realm of developing novel anti-cancer drugs. Their seminal work in Nature Immunology 2005 reported the discovery of a new target protein called FROUNT, which is linked to regulation and movement of the TAMs.

Since FROUNT amplified "chemokine signaling," a type of cellular communication, an integral process for TAM accumulation and activity, it was therefore linked directly to TAM regulation.

The team decided to expand on these findings, in order to investigate whether a therapeutic strategy can be formulated and have published their findings in Nature Communications. Through animal experiments, the researchers found that by regulating FROUNT expression in TAMs, cancer growth could be suppressed.

Then, in order to reduce any side effects, the team also developed an independent strategy of limiting the effect of FROUNT on chemokine signaling by inhibiting the interaction between the two. The team screened 131,200 compounds and zeroed in on disulfiram, a drug used to treat alcoholism, and known for its potential as an anti-cancer drug. This drug was found to directly bind to the FROUNT site, making FROUNT unavailable for interaction with the components of chemokine signaling.

Reflecting on the results, Terashima explains, "When tested on mice, disulfiram inhibited the movement of macrophages and suppressed the growth of cancer cells. Therefore, our findings present a new cancer treatment strategy that can suppress the growth of cancer cells that are difficult to respond to by immune checkpoints when used in combination with disulfiram."

The team is now further pushing the boundary of the finding and has started clinical research at the National Cancer Center Hospital East. Illustrating the outline for further research, Terashima comments, "since macrophages pose as a problem in various types of diseases, the indications for FROUNT inhibitors for a wide range of diseases may be considered."

Indeed, the team expects this this to be the first therapeutic strategy to regulate TAMS, and are hopeful that a better understanding of the correlation between the inhibition of the target protein FROUNT and TAMs paint a promising picture for the future of novel therapeutic strategies.

###

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of "Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Dr. Terashima from Tokyo University of Science

Dr. Yuya Terashima is a junior associate professor at the Department of Biological Sciences, Tokyo University of Science. He discovered a chemokine signal regulator FROUNT which directly binds to the receptor, and has been studying for the family of the chemokine-receptor associating molecule, aiming for therapeutic applications of their functional inhibitors. He works with his team to understand the molecular mechanisms of living organisms with a specific perspective on inflammation and immunology, and drug discovery.

Funding information

This study was supported in part by Practical Research for Innovative Center Control (JP19ck0106422) and Project for Cancer Research and Therapeutic Evolution (P-CREATE, JP19cm0106204) from the Japan Agency for Medical Research and Development (AMED) and JSPS KEKENHI.

Tsutomu Shimizu | EurekAlert!
Further information:
http://dx.doi.org/10.1038/s41467-020-14338-5

More articles from Life Sciences:

nachricht Biophysicists reveal how optogenetic tool works
29.05.2020 | Moscow Institute of Physics and Technology

nachricht Mapping immune cells in brain tumors
29.05.2020 | University of Zurich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Black nitrogen: Bayreuth researchers discover new high-pressure material and solve a puzzle of the periodic table

29.05.2020 | Materials Sciences

Argonne researchers create active material out of microscopic spinning particles

29.05.2020 | Materials Sciences

Smart windows that self-illuminate on rainy days

29.05.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>