The study also found higher levels of the JAK2 gene in patients with the EBV-positive subtype, suggesting that certain gastric cancers could be susceptible to JAK2 inhibitors, such as ruxolitinib. However, at this point, studies are not currently examining JAK2 inhibition in this disease type. An earlier study did explore AZD1480 with gastric cancer; however, development of this compound was discontinued.
Amplifications in PD-L1/2 in the EBV-positive subtype indicate that checkpoint inhibitors directed toward these ligands could be effective. A phase I study is investigating the PD-L1 inhibitor MPDL3280A in patients with solid tumors or hematologic malignancies. Patients with gastric cancer will be enrolled in this study, although it is not specifically looking for the EBV-positive subtype. The chromosomally unstable category represented the largest subtype, with these tumors generally being located in the areas between the stomach and esophagus. Bass noted that these tumors have a striking number of genomic amplifications of key cancer-promoting genes.
This finding result opens up an entirely new line of research to allow us to investigate what underlies this deadly form of gastric cancer and to ultimately develop new therapies. The NCI and the National Human Genome Research Institute, which are run by the National Institutes of Health (NIH), manages TCGA. In a press release concerning the results, the director of the NIH characterized the EBV findings as groundbreaking.
This study reinforces the value of the approach we are using to study genomic diversity and similarity among tumors of many different cancer types. Only such a systematic analysis could have yielded observations about the association between EBV and several provocative molecular characteristics.