Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell surface transporters exploited for cancer drug delivery

03.12.2012
Whitehead Institute scientists report that certain molecules present in high concentrations on the surfaces of many cancer cells could be exploited to funnel lethal toxic molecules into the malignant cells. In such an approach, the overexpression of specific transporters could be exploited to deliver toxic substances into cancer cells.

Although this finding emerges from the study of a single toxic molecule and the protein that it transports, Whitehead Member David Sabatini says this phenomenon could be leveraged more broadly.

"Our work suggests a different strategy for cancer therapy that takes advantage of the capacity of a cancer cell to take up something toxic that a normal cell does not," says Sabatini, who is also a professor of biology at MIT and a Howard Hughes Medical Institute (HHMI) investigator. "As a result, that toxic molecule would kill the cancer cell. By identifying transporters on the surface of cancer cells, you might be able to find a molecule that a specific transporter would carry into the cell, and that molecule would be toxic to that cell. You really could have something that's much more selective to cancer cells."

The Sabatini lab's research is published online today in the journal Nature Genetics.

Kivanc Birsoy, a postdoctoral researcher in Sabatini's lab and first author of the Nature Genetics paper, used a special line of haploid cells developed by former Whitehead Fellow Thijn Brummelkamp to screen for genes that assist cellular entry of 3-bromopyruvate's (3-BrPA), a potential cancer drug in clinical development. 3-BrPA is thought to work by inhibiting glycolysis, a cellular process that releases energy by splitting glucose molecules. Because many cancer cells are heavily dependent on the upregulation of glycolysis, drugs that interrupt this pathway may be effective in targeting these glycolytic cancer cells.

From the screen and massively parallel sequencing, Birsoy identified the gene that codes for the protein monocarboxylate transporter 1 (MCT1), which is necessary and sufficient for 3-BrPA's transport into cells, where the toxic molecule ultimately kills them. In fact, the level of MCT1 on the surface of glycolytic tumor cells is a predictor of those cells' sensitivity to 3-BrPA—the higher the cells' expression of MCT1, the more sensitive they are to 3-BrPA. This holds true in in vitro and in vivo models across multiple lines of human cancer cells.

The correlation between MCT1 concentration and 3-BrPA sensitivity could be used to help determine how certain malignant tumors are treated.

"This study makes MCT1 a biomarker for 3-BrPA," says Birsoy. "So in the future, if 3-BrPA is approved as a drug, presumably you could predict if a patient's cancer tumor is going to be sensitive by looking at the levels of this molecule. No tumor without MCT1 would respond to treatment with 3-BrPA."

This work was supported by the National Institutes of Health (CA103866), the David H. Koch Institute for Integrative Cancer Research, the Jane Coffin Childs Memorial Fund, and the National Science Foundation (NSF).

Written by Nicole Giese Rura

David Sabatini's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute investigator and a professor of biology at Massachusetts Institute of Technology.

Full Citation:

"MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors"

Nature Genetics, December 2, 2012, online.

Kivanc Birsoy (1,2), Tim Wang (1), Richard Possemato (1,2), Omer H Yilmaz (1,2), Catherine E Koch (1,2), Walter W Chen (1,2), Amanda W Hutchins (1,2), Yetis Gultekin (1,2), Tim R Peterson (1,2), Jan E Carette (1,6), Thijn R Brummelkamp (1,6), Clary B Clish (3) and David M Sabatini (1).

1. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.

2. Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.

3. Broad Institute, Cambridge, Massachusetts, USA.
4. David H Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts, USA.

5. Howard Hughes Medical Institute, MIT, Cambridge, Massachusetts, USA.
6. Present addresses: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA (J.E.C.) and Department of Biochemistry, Netherlands Cancer Institute, Amsterdam, The Netherlands (T.R.B.)

Nicole Rura | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>