Since the 1980s, many studies have focused on the use of a light-based cancer treatment known as photodynamic therapy (PDT). The magic ingredient in this innovative treatment strategy is a light-sensitizing agent, or photosensitizer, which is illuminated by light in the presence of oxygen. Research has shown that the proper blend of light, oxygen, and photosensitizer may lead to the complete elimination of a wide range of cancers.
How can shining light on a tumor lead to its eradication? Simply put, the photosensitizer enables the transfer of energy from light to oxygen, resulting in the generation of highly unstable and reactive oxygen molecules. These molecules can damage cancer cells in ways that not only shrink tumors, but also activate the immune system to eliminate those deadly clusters of cells known as metastases.
In recent years, the pharmaceutical industry has been scrambling to identify novel photosensitizers in order to determine which ones will work best against cancer. At this time, only a few of these light-sensitizing agents have been approved for cancer treatment.
Photosensitizers vary in the ways they are metabolized by the body. The ideal agent is taken up easily by cancer cells and retained within the tumor while being cleared fairly easily from normal tissues. When the concentration of the photosensitizer is much higher in malignant than in normal tissues, this can result in the targeted destruction of the tumor, with virtually no side effects.
Leiden Studies of Bremachlorin-PDT Shed New Light
Cancer research at two academic centers in The Netherlands—Leiden University Medical Center (LUMC) in Leiden, and Erasmus University Medical Center in Rotterdam—has provided new insights into the tumor-killing power of PDT. Dutch scientists from these institutions recently sought to compare the utilization of two photosensitizers by mouse tongue tumors in contrast with normal tongue tissue.
One of these agents was Chlorin e6, which has been studied for over two decades and is known to target the tumor’s blood vessel supply. The other agent was Bremachlorin, which contains Chlorin e6 as well as two other components that, in principle, should boost the agent’s tumor-killing power.
The Dutch researchers found that both Bremachlorin and Chlorin e6 were taken up and retained by tumor tissues (oral squamous cell carcinomas) much more than normal tissues. Nevertheless, Bremachlorin displayed a more lasting therapeutic potential. Whereas Bremachlorin was selectively concentrated in tumor tissues at 48 hours, no Chlorin e6 could be detected at that point in time. These research findings were reported in the January 2014 Journal of Biomedical Optics and also in the March 2014 issue of Lasers in Surgery and Medicine.
In their second report, the authors noted that Chlorin e6 is rapidly excreted by the body. This rapid clearance helps to avoid what has been the hallmark side effect of PDT: a strong skin sensitivity to sunlight (photosensitivity), causing discomfort that can last for days or even weeks. Even though Bremachlorin consists of about 80% Chlorin e6, the agent remains in the tumor tissue for much longer periods of time (when compared to pure Chlorin e6), and no photosensitivity reactions have been observed following the Bremachlorin-PDT sessions .
Research Needed to Optimize Bremachlorin-PDT
Bremachlorin’s ability to accumulate preferentially in tumors may allow for selective targeting of those tumors. This agent’s true potential will need to be assessed by conducting well-designed clinical trials. The LUMC-Erasmus researchers propose that such findings can be used to define an optimal protocol for using Bremachlorin in photodynamic treatments.
Cancers of the skin, bladder, brain, breast and lung are just a few of the cancers that could be studied in the context of Bremachlorin-PDT. Skin cancer has received the lion’s share of clinical trial attention for the simple reason that, in general, it’s easier to study skin cancer than most other cancers. Nevertheless, there is growing excitement about the possibility of treating the more common solid tumors as well, with breast cancer being a prime example.
“What we’ve seen in our preliminary studies of breast cancer is that Bremachlorin is taken up very actively by the breast cancer cells and stays in the tumor far longer than can be achieved with other photosenstiizers,” says Clemens Lowik, PhD, one of the LUMC investigators. “Since it’s taken up by tumor cells and retained much longer than the usual six or seven hours, you are more likely to see better tumor eradication. Along with the lack of side effects, this suggests great potential for using Bremachlorin-based PDT to treat breast cancer as well as other tumor types.”
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