Targeting Cancer Stem Cells with Light

MNM | October 22, 2014 | Discoveries | No Comments

Cancer continues to be a very deadly disease, with well over 8 millions deaths worldwide in 2012. Although some progress has been made in cancer treatment, the ability to promote long-term survival after a diagnosis of advanced cancer has been limited.

Recent studies suggest that the solution may lie in targeting a group of biologically unique cells, called cancer stem cells (CSCs), exists within most tumors and may be responsible for tumor growth, progression, metastasis, and even relapse. These are the same cells that tend to survive chemotherapy and radiotherapy, planting the seeds for a future recurrence. Similarly, any CSCs that are missed by surgery are the ones that spawn a deadly recurrence later on.

As our understanding of CSCs has improved, much research has been directed at therapeutic strategies that could potentially target these cells. Photodynamic therapy, or PDT, is a potentially curative treatment for various types of cancer. This therapy involves the transfer of energy from an excited photosensitizer (light-sensitizing agent) to oxygen molecules in order to produce a singlet oxygen species, which in turn helps destroy malignant cells.

New Light on Targeting Cancer Stem Cells

A number of studies of PDT have suggested considerable potential for eliminating CSCs. For example, three recent reports provide the following conclusions:

Head and neck cancers are notoriously resistant to chemotherapy. Following PDT, highly tumor-promoting CSCs in head and neck cancer became sensitive to conventional chemotherapy. The researches concluded that, by specifically eliminating CSCs, PDT may serve as a potent adjunct to chemotherapy against head and neck cancer, as reported in the 24 January 2014 issue of PLoS One.
The encapsulation of photosensitizer, methylene blue, in alginate-based nanoparticles, can help amplify the photodynamic reaction. Nanoparticle encapsulated methylene blue has the capacity to eliminate CSCs under low-oxygen conditions, an important goal of current cancer therapy, as reported in the 25 July 2014 issue of Molecular Pharmacology.
Researchers from the University of Mumbai in Mumbai, India, recently concluded that these nanocarriers have potential to improve the selective targeting of CSCs, thus helping to overcome problems such as dose-limiting side effects, high drug doses, and emergence of multiple drug resistance with conventional chemotherapy, as reported in the 10 July 2014 issue of Frontiers in Pharmacology.

These reports suggest that the combination of photomedicine and nanotechnology may provide a golden combination for targeting the cancer stem cell populations, thus possibly helping to overcoming the serious limitations of conventional chemotherapy and radiotherapy. If this combination continues to show effectiveness in targeting these CSCs, there may come a day when conventional treatment is considered useless without the addition of this innovative light-based treatment strategy.

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Sources

Usacheva M, Swaminathan SK, Kirtane AR, Panyam J. Enhanced photodynamic therapy and effective elimination of cancer stem cells using surfactant-polymer nanoparticles. Mol Pharm. 2014 Jul 25. [Epub ahead of print]

Yu CH, Yu CC. Photodynamic therapy with 5-aminolevulinic acid (ALA) impairs tumor initiating and chemo-resistance property in head and neck cancer-derived cancer stem cells. PLoS One. 2014 Jan 24;9(1):e87129.

Kapse-Mistry S, Govender T, Srivastava R, Yergeri M. Nanodrug delivery in reversing multidrug resistance in cancer cells. Front Pharmacol. 2014 Jul 10;5:159.

Master A1, Malamas A, Solanki R, Clausen DM, Eiseman JL, Sen Gupta A. A cell-targeted photodynamic nanomedicine strategy for head and neck cancers. Mol Pharm. 2013 May 6;10(5):1988-97.

Mertins SD. Cancer stem cells: a systems biology view of their role in prognosis and therapy. Anticancer Drugs. 2014 Jan 10.