Nav: Home

Targeting a tumor trigger

March 15, 2017

Heidelberg, 15 March 2017 - Many cancer patients that receive chemotherapy go into remission at first, but relapse after treatment is discontinued. There is increasing evidence that this is due to the presence of cancer stem cells -- cells that reproduce indefinitely and may seed new tumors. A research group from Milan, Italy, now devised a strategy to specifically target cancer stem cells in some cancers and reduce their tumor-generating potential. The results are published today in EMBO Molecular Medicine.

Every tissue of our body has stem cells that continuously divide to replenish the body with new cells. In previous studies, the research team, headed by Pier Paolo Di Fiore and Salvatore Pece, investigated the role of a protein called Numb in maintaining stem cells in normal mammary gland development in mice. They found that Numb is required for cells to maintain the correct balance between stem cells and differentiated cells in the gland. Numb up-regulates p53, a protein that is known to arrest cell division. When Numb is lost, there is too little p53, resulting in more self-replicating stem cells. This may lead to the formation of tumors.

In many human breast cancers, Numb concentration is low and this is associated with a poor prognosis for the patients. In the present study, the researchers take a closer look at the role of Numb in these tumors. They find that tumors lacking Numb have increased numbers of cancer stem cells, thus providing the tumor with a higher potential to spread and grow. Moreover, the researchers found that p53 plays an essential role in this effect. When Numb concentration is low, p53 concentration will also drop. But when p53 levels are restored by blocking its degradation using a small chemical compound called Nutlin-3, the tumors are less aggressive and have fewer cancer stem cells. A number of drugs that target the p53 pathway, like Nutlin-3, are currently in clinical development.

Finally, the researchers tested the potential of combining Nutlin-3 and Paclitaxel, a common chemotherapy medication. While Paclitaxel treatment alone can lead to a decrease in tumor size, there is a large risk of relapse once the treatment is terminated. Combining Paclitaxel with Nutlin-3 not only potentiated the tumor response to Paclitaxel, but also prevented Numb-deficient tumors from re-growing after treatment discontinuation. This points to the potential of Nutlin-3 or similar drugs as treatment options to overcome chemoresistance due to cancer stem cells.

In the context of the current study, the researchers have developed a pre-clinical model system that specifically captures the impact of a treatment on cancer stem cells. All of their results are based on transplanting tumor cells from patients into mice and then using these mice in a variety of assays to investigate the presence of stem cells or the aggressiveness of the cancer. This system might be a valuable tool also in future experiments testing the impact of different compounds on cancer stem cells.

These pre-clinical findings suggest that breast cancer patients with a deficiency in Numb expression could become eligible for treatment with drugs similar to Nutlin-3 that are currently in clinical development. Exploiting the same pre-clinical model used for their studies, the researchers are testing the efficacy of this kind of drug candidates against cancer stem cells, and the possibility of identifying combination regimens with standard chemotherapies with minimized toxic effects, with the perspective of their possible application for the treatment of human breast cancer.
-end-
Pre-clinical validation of a selective anti-cancer stem cell therapy for Numb-deficient human breast cancers

Daniela Tosoni, Sarah Pambianco, Blanche Ekalle Soppo, Silvia Zecchini, Giovanni Bertalot, Giancarlo Pruneri, Giuseppe Viale, Pier Paolo Di Fiore and Salvatore Pece

Read the paper: http://embomolmed.embopress.org/content/early/2017/03/14/emmm.201606940

About EMBO

EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.

EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe.

For more information: http://www.embo.org

Contact:

Tilmann Kiessling
Head of Communications
Mobile: +49-160-90193839
E-mail: communications@embo.org

EMBO

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
More Stem Cells News and Stem Cells Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Teaching For Better Humans
More than test scores or good grades — what do kids need to prepare them for the future? This hour, guest host Manoush Zomorodi and TED speakers explore how to help children grow into better humans, in and out of the classroom. Guests include educators Olympia Della Flora and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#535 Superior
Apologies for the delay getting this week's episode out! A technical glitch slowed us down, but all is once again well. This week, we look at the often troubling intertwining of science and race: its long history, its ability to persist even during periods of disrepute, and the current forms it takes as it resurfaces, leveraging the internet and nationalism to buoy itself. We speak with Angela Saini, independent journalist and author of the new book "Superior: The Return of Race Science", about where race science went and how it's coming back.