Two adult cancer genes linked to Ewing sarcoma

Investigators from the University of Colorado Cancer Center (CO, USA) have discovered that alterations in the expression of the genes PIK3R3 and PTEN, usually found in adult tumors, are also found in Ewing sarcoma, a rare bone cancer found most commonly in young adults.

PTEN is a tumor suppressor gene that regulates a cell growth and survival pathway. Loss of PTEN can promote growth and survival of cells and thus this genetic alteration has been implicated in several cancers. In Ewing sarcoma, a rare cancer caused by the fusion of a gene on chromosome 11 with one on chromosome 22, very few alterations in oncogenes and tumor suppressors have previously been identified.

“Since this cancer is rare, there hasn’t been much financial incentive for pharmaceutical companies to develop new drugs to treat it. Identification of alterations common to adult tumors, in our case upregulation of PIK3R3 and loss of PTEN, could potentially allow us to adapt therapeutic strategies for adult cancers to treat Ewing Sarcoma,” commented Paul Jedlicka (University of Colorado Cancer Center).

Jedlicka’s team was originally investigating targets of miRNAs in Ewing Sarcoma until a graduate student realized that some cells had lost PTEN expression completely, and that most cell lines were also displaying varying expression levels of PIK3R3. The researchers then obtained real patient tumor sample and were able to confirm that these cells had a loss of PTEN.

“Another surprise was that when we tested the PTEN-positive and PTEN-negative cells against chemotherapies that are commonly used in Ewing sarcoma, we found cells that had lost PTEN were more resistant to vincristine,” Jedlicka continued. More studies will be required to look into this further, but using PTEN expression status as a biomarker could be an excellent tool for predicting vincristine response in Ewing sarcoma.

The other gene that was investigated in the studies was PIK3R3, which acts as a tumor promoter. This could be a therapeutic target in Ewing sarcomas that have elevated levels, to prevent excess growth. There are currently no drugs that can target this gene, but it has also been found to be present in some ovarian and colorectal cancers, as well as glioblastoma.

“Maybe if some pharma company develops a PIK3R3 drug for ovarian cancer or glioblastoma, it could be worth exploring its efficacy in Ewing’s as well,” Jedlicka suggested.

Source: Niemeyer BF, Parrish JK, Spoelstra NS, Joyal T, Richer JK, Jedlicka P. Variable expression of PIK3R3 and PTEN in Ewing sarcoma impacts oncogenic phenotypes. PLoS One 10(1), e0116895 (2015); University of Colorado Cancer Center press release