Light-Based Approach to Stomach Cancer

Photo (below, right) shows the successful treatment of stomach cancer using Bremachlorin-PDT, as presented by Dr. Vladimir Romanov in May 2013 at the 14th World Congress of the International Photodynamic Association in Seoul, South Korea.

 

It seems only natural to take one’s stomach for granted. When you eat, food travels down your esophagus and enters the stomach, where it gets churned up and broken down with the help of acidic juices. The partially digested food then enter your intestines, where the process of digestion is completed. From this vantage point, the stomach is just an intermediate train station on food’s journey through your body.

With a diagnosis of stomach cancer, however, this whole relationship with the stomach takes on a whole new meaning. Suddenly the chances of losing the stomach become a very real concern. In fact, most people who face a diagnosis of advanced stomach cancer will end up having most or all of the stomach removed by radical surgery (partial or total gastrectomy).

Even when this occurs, the risk of a relapse and death is quite large. In fact, stomach cancer is the second leading cause of cancer death worldwide. The high mortality rate is attributed to the typically late stage of diagnosis because the initial signs of the disease (occasional, indistinct belly pains) are too obscure to notice. Often the cancer is mistaken for an ulcer. For these reasons, stomach cancer is often detected only after it has reached an advanced, hard-to-treat stage.

In Southeast Asia, stomach cancer remains a tremendous challenge. This is partly because the incidence is very high compared to the rest of western world. Moreover, life expectancy is increasing in Japan and more broadly in urban areas throughout Asia, and thus the number of elderly people being treated for this cancer is steadily rising. But with increasing age, invasive treatments such as major surgery carry a much higher risk of complications as well as a greatly reduced quality of life. These trends have led to a strong and growing demand for less invasive treatments.

Photodynamic therapy (PDT) offers a noninvasive treatment option for people diagnosed with stomach cancer. The photodynamic approach entails the use of light-triggered chemical reactions—technically called photochemical reactions. These reactions are mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases. The photosensitizing agent is a substance that absorbs and transmits light’s energy in order to destroy abnormal or diseased cells.

 

Seeing the Cancer more Clearly

Part of the beauty of photodynamic methods is that the light-sensitizing agents (often chlorophyll derivatives) will concentrate selectively in the cancerous tissues. When those tissues are then exposed to light, they fluoresce or “glow”, so that the cancer becomes clearly visible. This technique, known as photodiagnosis or photodynamic diagnosis (PDD), can be used to help diagnosis cancer as well as to guide both PDT and surgery.

Researchers at Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, recently examined the possibility of using a photosensitizer to detect the presence of stomach cancer. For this purpose, they used a very well-studied agent called 5-aminolevulinic acid (ALA) during the operation in 21 patients with stomach cancer.

Before surgery, the ALA solution was given orally through a stomach tube. After each tumor was removed, it was assessed by a PDD system, and red fluorescence-positive lesions were compared with the pathological result (based on an analysis of the actual tumor tissue). Red fluorescence was found in 11 patients, and the specificity for detecting stomach cancer was considered to be 100%.

Just as importantly, the incidence of laparoscopic surgery was more than three times lower in the PDD-positive group than in PDD-negative cases. These findings indicated that PDD improved the sensitivity for the detection of peritoneal metastases and may be a useful technique for the preoperative staging of advanced stomach cancer, as reported in the May 2014 issue of Oncology.

The findings were confirmed by research out of Kochi Medical School in Kochi, Japan. This study found that “fluorescence navigation” by PDD provides good visualization of cancerous lesions and appears to be a promising diagnostic tool for stomach cancer. PDD can help differentiate high-grade dysplasia or stomach adenocarcinoma from normal tissue in the stomach—a potentially powerful tool for catching early-stage stomach tumors in high-risk populations. The approach appears to be especially useful for detecting the intestinal-type of stomach cancer, as reported in the March 2014 Journal of Surgical Oncology.

 

Possibilities for Photoimmune Treatment

Conventional photodynamic therapy (PDT) for cancer is limited by the lack of specificity or tumor-targeting ability of some photosensitizers. One strategy is to use a photosensitizer that is bound or conjugated to a human monoclonal antibody. The antibody works like a kind of guided missile that seeks out proteins found on the tumor’s surface. This antibody-assisted PDT strategy is also considered to be a form of photoimmunotherapy (PIT).

Researchers from Fukuoka University in Japan recently conducted a series of laboratory studies of this particular PIT approach. The antibody was specific for carcinoembryonic antigen, or CEA, a common target of immunotherapy strategies. Upon exposure to light, the CEA-positive stomach cancer cells were easily killed. In animal studies, a single PIT treatment, was shown to cause rapid destruction of cancer cells and marked inhibition of tumor growth.

Taken together, the new findings suggest that this antibody-based approach to PIT has great potential as an anticancer treatment for targeting CEA-positive tumors, as reported in the December 2014 International Journal of Cancer.

 

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Sources

Tsujimoto H, Morimoto Y, Takahata R, Nomura S, Yoshida K, Horiguchi H, Hiraki S, Ono S, Miyazaki H, Saito D, Hara I, Ozeki E, Yamamoto J, Hase K. Photodynamic therapy using nanoparticle loaded with indocyanine green for experimental peritoneal dissemination of gastric cancer. Cancer Sci. 2014 Oct 7. [Epub ahead of print]

Kishi K, Fujiwara Y, Yano M, Motoori M, Sugimura K, Ohue M, Noura S, Marubashi S, Takahashi H, Sakon M. Diagnostic laparoscopy with 5-aminolevulinic-Acid-mediated photodynamic diagnosis enhances the detection of peritoneal micrometastases in advanced gastric cancer. Oncology. 2014;87(5):257-65.

Namikawa T1, Inoue K, Uemura S, Shiga M, Maeda H, Kitagawa H, Fukuhara H, Kobayashi M, Shuin T, Hanazaki K. Photodynamic diagnosis using 5-aminolevulinic acid during gastrectomy for gastric cancer. J Surg Oncol. 2014 Mar;109(3):213-7.

Shirasu N1, Yamada H, Shibaguchi H, Kuroki M, Kuroki M. Potent and specific antitumor effect of CEA-targeted photoimmunotherapy. Int J Cancer. 2014 Dec 1;135(11):2697-710.

Romanov VA, Reshetnickov AV. PDT of stomach cancer with photosensitizer Bremachlorin^®: a pilot trial. The 14th IPA World Congress. May 28-31, 2013. Seoul, South Korea. Book of abstracts. 2013:53.

 

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