Breast Cancer Treatment with PDT: New Insights

Photodynamic therapy (PDT) is a noninvasive form of cancer therapy that has been successfully used to treat various types of cancer, and there has been growing interest in using this modality to treat advanced breast cancer.  In a recent study of PDT, scientists at the National Research Center in Cairo, Egypt,  used the light-sensitizing precursor called 5-aminolevulinic acid (ALA).  This natural substance is metabolized into protoporphyrin IX, which circulates in the body and preferentially accumulates within tumors.  Upon exposure to visible light, this substance triggers a series of reactions inside the tumor cells that lead to their eventual destruction.

The Cairo research team  was interested in testing the possibility that PDT could be used to enhance the efficacy of conventional anti-cancer drugs.  Doxil®, an active chemotherapy drug often used in treating metastastic breast and ovarian cancer, is a nano-formulation of the drug doxorubicin.  At the standard high doses, however, Doxil® can have some undesirable side effects, such as fatigue, shortness of breath, and damage to the heart.

The researchers observed that ALA-PDT interacted with low doses of Doxil® in a synergistic manner to destroy breast cancer cells.  Combining PDT with low doses of chemotherapy could result in therapeutically favorable effects on the immune system, since both PDT and low-dose chemotherapy tend to bolster  the anti-cancer immune defenses, as reported last year in the International Journal of Cancer.  Clinical studies are needed to assess these potent therapeutic interactions in cancer patients.

How PDT Causes the Death of Cancer

In a separate study conducted at the University of Johannesburg in Doornfontein, South Africa, researchers found that PDT was highly effective in bringing about  “programmed cell death” in breast cancer cells, as reported in the 24 March 2014 issue of Photomedicine and Laser Surgery.  This cell-death process is also known as apoptosis, and it is the fundamental mechanism by which high-dose chemotherapy and radiotherapy also kill cancer cells.

Within the living human body, however, PDT  is able to slowly break down and ultimately destroy the tumor mainly through the natural cell-death process known as necrosis.  As has been reported by Dr. Michael Hamblin and his colleagues at the Wellman Center for Photomedicine in Boston (USA), this process results in the effective stimulation of the very anti-cancer immune mechanisms needed to eliminate cancer cells that manage to resist chemotherapy, thus persisting after the treatment.

In this way, PDT could be used around the time of chemotherapy to circumvent the seemingly intractable problem of chemoresistance—a problem that has long plagued modern oncology because it enables the progression of this deadly disease.  Much research is now underway to test the combination of PDT with various anticancer drugs.  The hope is that such combinations will enhance the effectiveness of those drugs while also bolstering the immune system’s ability to eliminate any cancer cells that manage to survive after drug treatment.

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Sources

Zakaria S1, Gamal-Eldeen AM2, El-Daly SM3, Saleh S4. Synergistic Apoptotic Effect of Doxil® and Aminolevulinic Acid-Based Photodynamic Therapy on Human Breast Adenocarcinoma Cells. Photodiagnosis Photodyn Ther. 2014 Mar 13 [Epub ahead of print]

Mfouo-Tynga I1, Houreld NN, Abrahamse H. Induced Cell Death Pathway Post Photodynamic Therapy Using a Metallophthalocyanine Photosensitizer in Breast Cancer Cells. Photomed Laser Surg. 2014 Mar 24. [Epub ahead of print]

Nars MS1, Kaneno R. Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy. Int J Cancer. 2013 Jun 1;132(11):2471-8

Mroz P, Hashmi JT, Huang YY, Lange N, Hamblin MR.   Stimulation of anti-tumor immunity by photodynamic therapy. Expert Rev Clin Immunol. 2011 Jan;7(1):75-91.

Castano AP, Mroz P, Wu MX, Hamblin MR.  Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model. Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5495-500

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