Photodynamic Solutions for Breast Cancer

Women with metastatic breast cancer are often faced with a serious dilemma: The five-year survival rate is a dismal 2%, and standard treatments for these advanced-stage breast cancers are replete with toxic side effects that can make life miserable. Many chemotherapy drugs, for example, can raise the risk of life-threatening heart disease as well as a variety of immune, digestive, kidney, bone and brain problems. Common side effects include fatigue, nausea, vomiting, hair loss, mouth sores, a tendency to bruise or bleed easily, poor appetite, low blood cell counts, and greater risk of infections.

Against this backdrop, you’d think that more and more oncologists would be interested in embracing the non-toxic light-based modality called photodynamic therapy, or PDT. In PDT, a photosensitizing agent is triggered by a specific wavelength of light to induce the death of cancer cells. Like surgery, PDT can remove the primary tumor, but it does so without damaging the normal tissues. And like chemotherapy, PDT can be used to help eradicate deadly metastases, again without harmful side effects.

In short, PDT offers a novel way to treat cancers without surgery, radiotherapy or chemotherapy. But it would be oversimplistic to say that PDT can replace these long-established mainstream treatments. To begin with, it’s difficult to destroy larger tumors with PDT alone. In these cases, either surgery or radiotherapy (or both) also may be needed. In tandem with surgery, PDT can be used to eliminate cancer cells that may be left over following the operation. With the two other treatments, PDT can work synergistically to break down tumors, thus reducing the amount of chemo and radiation needed for effective treatment.

The key point is that PDT can make up for many of the deficiencies of mainstream cancer treatments. Let’s take a look at what recent research suggests along these lines for women facing a diagnosis of breast cancer. In most situations, PDT is being combined with conventional treatments in ways that make those treatments more humane and ultimately more effective.

Integrating PDT into Breast Cancer Treatment

These days, the vast majority of breast cancer patients are first treated with some form of surgery, which consists of either lumpectomy or mastectomy. After this, several other treatments—radiotherapy, chemotherapy, or hormonal therapy—are used as adjuvants to help eliminate any residual disease. All of these treatments can have side effects, and this is one of the reasons non-toxic innovative therapies are urgently needed.

Researchers at the National University of Río Cuarto (Argentina) recently reviewed a variety of ways in which PDT can be integrated into breast cancer treatment. They concluded that PDT can work synergistically with both radiotherapy and chemotherapy, as well as possibly reducing the need for surgery.

With regard to radiotherapy, for example, they state the following in the December 2014 World Journal of Clinical Oncology: “The interaction of PDT and ionizing radiation could enhance the therapeutic effect, thus reducing the dose of radiation dose and potential side effects.”

The synergisms between PDT and both chemotherapy and radiotherapy could result in a range of favorable outcomes, such as the following:

• increasing the overall efficacy of chemo and radiotherapy
• decreasing the dosage of both treatments, thus reducing toxicity
• minimizing the likelihood of developing drug resistance

All of these benefits make PDT a prime candidate for the future treatment of breast cancer. The Río Cuarto team proposes developing a rational design for effective combination regimens. They contend that such a rational design can best be achieved by improving our understanding of the mechanisms and molecular interactions of PDT with the other treatment modalities.

A good example of this combination strategy is the chemotherapy drug beta-lapachone, a medicine derived from the Purple Lapacho or Pau d’Arco tree of South America. A recent laboratory study by the Río Cuarto team found that this agent synergistically increased the effectiveness of PDT for breast cancer 24 hours after the light treatment.

The improvement was linked to a photodynamic effect on a specific component of the beta-lapachone that blocks with the progression of breast cancer. Thus, the combined use of PDT with beta-lapachone offers a promising approach to this life-threatening disease. As you can see, a drug that appears to have great cancer fighting potential can become even more powerful when used as part of the photodynamic approach.

Blending PDT with Natural Products

For thousands of years, plants have served as medicine for humans. And for the past several decades, traditional medicinal plants have been used as lead compounds for drug discovery in cancer medicine. For example, the drug Taxol is derived from the bark of the Pacific yew tree (Taxus brevifolia) and is used in the treatment of breast cancer and other cancers.

Both PDT and plant-derived drugs trigger the death of cancer cells by a variety of mechanisms. Both can be used in tandem for an even stronger tumor-killing effect, as reported online ahead-of-print on 25 October 2015 in Anticancer Agents in Medicinal Chemistry.

Though PDT is known for its ability to eliminate chemoresistant and radioresistant cells—that is, cancer cells that survive after chemotherapy and radiotherapy, respectively—there are some situations in which resistance to this light-based therapy may develop. Scientists have identified a few key mechanisms by which cancer cells may acquire such resistance, and this has led to an exploration of strategies to target those same mechanisms.

For example, the anticancer drugs Gleevec and Iressa both appear to block the pumping mechanism by which cancer cells eliminate the photosensitizing agents (porphyrins) used in PDT. A similar purpose can be served by using natural products, such as soy genistein. Available as a dietary supplement, soy genistein (also known as an isoflavone), has been shown to inhibit BCL-2, a key protein that may reduce the effectiveness of PDT against some cancers. Soy genistein could therefore further boost the effectiveness of PDT against the more aggressive forms of breast cancer, as reported in the 21 January 2010 Journal of Photochemistry & Photobiology B.

Another example is Aloe emodin, a natural product obtained from the Aloe vera plant. In addition to its strong laxative effects, Aloe emodin is regarded as a new type of anticancer agent with selective activity against various types of tumors.  This agent’s usefulness as part of PDT was recently confirmed in laboratory studies at the First Affiliated Hospital of Chongqing Medical University, in Chongqing, China.  

The scientists found that, in the context of PDT, Aloe emodin significantly inhibited the invasion and metastatic processes of breast cancer cells. The Chongqing reseachers propose that Aloe emodin should be considered a new photosensitizer in PDT for breast cancer, as reported on 20 August 2015 in the online ahead-of-print edition of Anticancer Agents in Medicinal Chemistry.

Bremachlorin-PDT for Breast Cancer

In closing, let’s consider the photosensitizing agent Bremachlorin, which is derived from the freshwater algae called Spirulina platensis. Clinically approved in Russia under the name Radachlorin, this agent has now been evaluated extensively in at least 15 clinical studies. Researchers have increasingly turned their attention to the possibility that Bremachlorin could be used in combination with radiotherapy and other mainstream treatments for breast cancer.

In the most recent study, scientists at Tehran University of Medical Sciences in Iran examined the effects of Bremachlorin as a sensitizer in both photodynamic and radiation therapy for human breast cancer.  The laboratory findings showed that, whereas Bremachlorin had no significant cancer-killing effects by itself, it had a potent killing effect on breast cancer cells when activated by light.

In addition, although Bremachlorin did not act as a radiosensitizer, the combination of Bremachlorin-PDT with radiotherapy resulted in a significant increase in the killing of breast cancer cells when compared to either treatment alone.  This is an important finding for a variety of reasons, including the option to reduce the dose of radiation and to increase the acceptability of PDT as an adjunct to radiotherapy.

The Tehran authors conclude that this integration of radiotherapy with Bremachlorin-PDT may offer “…a worthwhile approach for breast cancer treatment. It appears that we can reduce the adverse effects of treatments without reducing the efficacy of therapy.” In other words, this logical light-based approach may enable us to finally attain a saner, more effective level of treatment for this dread disease.

Sources

George BP, Abrahamse H. A review on novel breast cancer therapies: Photodynamic therapy and plant derived agent induced cell death mechanisms. Anticancer Agents Med Chem. 2015 Oct 25. [Epub ahead of print]

Chena Q, Tiana S, Zhub J, Lia KT, Yuc TH, Yub LH, Bai DQ. Exploring a novel target treatment on breast cancer: aloe-emodin mediated photodynamic therapy induced cell apoptosis and inhibited cell metastasis. Anticancer Agents Med Chem. 2015 Aug 20. [Epub ahead of print]

Lamberti MJ, Vittar NB, Rivarola VA. Breast cancer as photodynamic therapy target: Enhanced therapeutic efficiency by overview of tumor complexity. World J Clin Oncol. 2014 Dec 10;5(5):901-7.

Ghoodarzi R, Changizi V, Montazerabadi AR, Eyvazzadaeh N. Assessing of integration of ionizing radiation with Radachlorin-PDT on MCF-7 breast cancer cell treatment. Lasers Med Sci. 2015 Dec 21. [Epub ahead of print]

Qiao Z, Wang J, Wang H, Liu X, Li R. Inhibition of breast cancer cell proliferation by a newly developed photosensitizer chrolophyll derivative CPD4. Int J Clin Exp Med. 2015 May 15;8(5):7381-7.

Ferenc P, Solár P, Kleban J, Mikes J, Fedorocko P. Down-regulation of Bcl-2 and Akt induced by combination of photoactivated hypericin and genistein in human breast cancer cells. J Photochem Photobiol B. 2010 Jan 21;98(1):25-34.