New molecule with anti-cancer and anti-metastatic properties

September 4, 2012
Liminib stabilizes the microtubules. Microtubules are filamentous structures that can be visualized using specific antibodies. Thus, in a same cell, the total microtubules can be on labeled in red and the stabilized microtubules in green. Unlike the control cells, numerous green, stabilized microtubules can be observed in the Liminib treated cells. The scale bar (in white, bottom right hand photo) represents 10 µm. © Lafanechère/CNRS

A new molecule with anti-cancer and anti-metastatic properties has been discovered by teams from CNRS, CEA, the Institut Curie and Inserm, in collaboration with Australian and British researchers. This anticancer drug acts on cells resistant to conventional chemotherapy thanks to an entirely novel action mechanism. It targets not only the multiplication of cells but also their mobility and thus could prevent the formation of metastases. Published in Cancer Research, the results obtained in vitro and on animals could, in the medium term, lead to the development of alternative anti-cancer treatments.

The appearance of resistant tumors considerably limits the efficacy of conventional chemotherapy treatments. In addition, the dissemination of metastases is the most frequent cause of death of patients suffering from cancer. It is for this reason that the researchers explored various , particularly the development of that are active on resistant cancers and which prevent the formation of metastases.

It took nearly ten years for a group of biologists and chemists from CNRS, CEA, the Institut Curie and , in collaboration with Australian and British scientists, to succeed in their quest of discovering and characterizing a new anti-cancer and anti-metastatic molecule. To do so, the researchers used a robotic high-throughput screening platform: nearly 30,000 molecules were tested until one from the chemical library of the Institut Curie exhibited the sought-after activity on tumorous cells and was thus selected. Known as Liminib (or Pyr1), this new molecule has been identified as an inhibitor of LIM Kinase (LIMK). Overexpressed in invasive carcinoma, LIMK represents a relevant that is generating considerable interest in numerous laboratories. This kinase is known to regulate the dynamic of the internal skeleton of the cell, constituted of a network of fibers, including filaments of actin and microtubules that allow the cells to move and multiply, two properties actively used by cancerous cells.

Liminib is thus the first LIMK inhibitor discovered that exhibits anti-cancer properties. This molecule blocks the mobility of the cells by disorganizing the cytoskeleton of actin and also brings about a stabilization of the microtubular network, thereby preventing the cells from multiplying, through a mechanism different to that of Taxol, a widely used anti-cancer drug. The researchers show that Liminib is toxic to several cancerous cell lines in vitro, including cell lines resistant to chemotherapy. In addition, the results of a "pilot" preclinical study conducted on a mouse model are encouraging: they reveal not only good efficacy but also good tolerance to the new molecule. In the medium term, this work could lead initially to the development of alternative treatments for patients for whom therapy is no longer an option.

Explore further: Cell discovery strengthens quest for cancer treatments

More information: Pharmacological inhibition of LIM Kinase stabilizes microtubules and inhibits neoplastic growth. Prudent R, Vassal-Stermann E, Nguyen CH, Pillet C, Martinez A, Prunier C, Barette C, Soleilhac E, Filhol O, Beghin A, Valdameri G, Honore S, Aci-Seche S, Grierson D, Antonipillai J, Li R, Di Pietro A, Dumontet C, Braguer D, Florent JC, Knapp S, Bernard O, Lafanechère L. - Cancer Research (online since the 3 July 2012. The paper version is due to be published in September 2012)

Related Stories

Cell discovery strengthens quest for cancer treatments

February 13, 2012
Fresh insights into how our cells multiply could help scientists develop drugs to treat cancer.

Researchers find drug duo kills chemotherapy-resistant ovarian cancer cells

December 7, 2011
The use of two drugs never tried in combination before in ovarian cancer resulted in a 70 percent destruction of cancer cells already resistant to commonly used chemotherapy agents, say researchers at Mayo Clinic in Florida. ...

Researchers identified a protein useful in predicting the risk of pulmonary metastases in breast cancer patients

April 10, 2012
Researchers from the Bellvitge Biomedical Research Institute (IDIBELL) have shown that breast cancer cells that metastasize to the lung express a higher level of the protein peroxiredoxin 2 (PRDX2). The study suggests that ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.