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Combined gene transduction and light therapy targets gastric cancer

Researchers report photoimmunotherapy to be effective against elusive gastric cancer cells following transduction with the gene that expresses the extracellular domain protein of HER2. The results are published in the journal Small Molecule Therapeutics.

“Gastric cancer is one of the most common malignancies worldwide, making it the third leading cause of cancer-related death,” explain Michihiro Ishida, Shunsuke Kagawa and colleagues at Okayama University Graduate School of Medicine and Okayama University Hospital in Japan in a recent report. In particular they note the pernicious nature of the most common form of gastric cancer metastasis, which occurs in the peritoneum – the membrane surrounding the abdominal cavity. The researchers’ latest work targets some of the limitations of existing gastric cancer therapies, such as targeting challenges and the development of resistance to anticancer drugs.

The only known target for gastric cancer is the protein human epidermal growth factor receptor 2 (HER2). However expression of this protein tends to be low in gastric cancers and is particularly low in peritoneal cancers. To tackle this obstacle the researchers devised a viral vector that transducts into HER2-negative cells with genes expressing the extracellular domain protein for HER2. They showed the approach was effective in samples with mixed HER2-positive HER2-positive cells, as would likely be the case in peritoneal cancers.

Bioluminescence images of tumor bearing mice after treatment
The time course of the bioluminescence images of tumor bearing mice after treatment in vivo for: no treatment – control; treated with Trastuzumab-IR700 (Tra-IR700) mediated photoimmunotherapy (PIT) – IR+PIT; treated with HER2-extracellular domain transducing adenovirus (Ad/HER2-ECD) mediated PIT – Ad + PIT; and treated with Ad/HER2-ECD with Tra-IR700-mediated PIT – Ad+ IR+PIT; one dose – X1; three doses – X3
Image: Okayama University