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Shining a New Light on Cancer

December 10, 2015

Shining a New Light on Cancer

The Lack of Specificity

It is hard to treat something you cannot see. Early-stage cancer is a perfect example. Cell-to-cell interaction is at the very foundation of human biology. It is responsible for cell growth, motility, the development of our immune system, and yes, even such deadly diseases as cancer. In many respects, it is the most fundamental determinant of life—and death. 1 This year alone in the U.S, some 1.6 million men and women will be diagnosed with cancer. More than a third of them will die from the disease. 2

The trouble is cell-to-cell interactions are nearly impossible to visualize for any length of time or over any spatial distance throughout living organisms. Even the most sensitive medical imaging systems have trouble seeing cell-to-cell interactions. The density and natural fluorescence of living tissue pose two major problems. So does a phenomenon called photobleaching, which is a photochemical alteration of a dye or a fluorophore molecule that permanently disables its ability to fluoresce. 3

The result is a huge void in cellular medicine. For all practical purposes, researchers and clinicians are unable to study live cell-to-cell activity beyond what they can see through a microscope. Even then, the view is short lived, since the lifespan of extracted living cells is measured in hours. That leaves various chemotherapy and radiation treatments unable to specifically target diseased cancer cells. Instead, clinicians administer larger doses of these therapies, which are often toxic to surrounding tissue. Coping with the myriad side effects, patients and clinicians alike sometimes wonder if the cure is not worse than the disease itself. 4

Cancer Suicide Gene Therapy Can Now “See” Its Targets

The ultimate goal of cancer therapy is to eliminate diseased cells while leaving all healthy cells intact. In the past few years, one of the most promising new cancer strategies that aims to accomplish that is called cancer suicide gene therapy (CSGT). Like those therapies before it, CSGT has been limited by its ability to deliver therapeutic transgenes, which are foreign genes taken from one source and directly introduced into another, in this case cancer cells. 5 At least, that is, until now.

Scientists from several global research facilities, including PerkinElmer’s Life Sciences Research Center in Hopkinton, MA, recently announced the creation of a bioluminescent probe they call NCL, short for Nitroreductase Caged Lucifrerin. The probe is the first of its kind for use in non-invasive, real-time imaging of a family of related proteins used to develop antibiotics and in enzyme therapyGDEPT, which is the so-called suicide gene therapy of choice in treating cancer. 6

Based on fluorescent CytoCy5S, NCL has been used successfully to image live bacteria and mammal cells, as well as in preclinical models of cancer and bacterial infection, says Kevin P. Francis, Vice President, Biology Solutions for PerkinElmer and one of the principal researchers on the project. In addition to providing some of the cell lines used by the scientists over the course of their research, Francis says that both PerkinElmer IVIS® Spectrum and IVIS®-100 imaging systems were used extensively over the course of the research project to measure the amount of bioluminescent imaging signal production in cell cultures, bacteria, and in mice. 7

A Potential Game Changer

“The results of our research demonstrate that the new NCL probe can be effectively used for non-invasive, real-time imaging in vitro, in live bacteria and mammalian cells, as well as in preclinical models of cancer and certain bacterial infections,” Francis says. “We believe this innovative reagent will significantly simplify the screening process and accelerate the development of new cancer therapies based on enzymes and other fields where protein expression is important.”


  1. Ronald N. Germain, Ellen A. Robey, and Michael D. Cahalan, “A Decade of Imaging Cellular Motility and Interaction Dynamics in the Immune System,” Science, 29 June 2012: 336 (6089), 1676-1681.
  2. Frontiers in Suicide Gene Therapy of Cancer, U.S. National Library of Medicine, National Institutes of Health.
  3. A “Caged” Luciferin for Imaging Cell–Cell Contacts, Journal of the American Chemical Society, 2015, 137 (27), pp 8656–8659. Published online June 2015.
  4. Chemotherapy: When the Cure Seems Worse than the Disease, The Washington Diplomat, Published online February 2015. See also, Fraught With Risks and Side-Effects, Cancer
  5. Frontiers in Suicide Gene Therapy of Cancer, U.S. National Library of Medicine, National Institutes of Health.
  6. Strategies for Enzyme/Prodrug Cancer Therapy, Clinical Cancer Research, November 2001 7; 3314.
  7. Development of a Bioluminescent Nitroreductase Probe for Preclinical Imaging, U.S. National Library of Medicine, National Institutes of Health.

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