Drug Combination Shows Promising Outcomes against Ewing Sarcoma
Ewing sarcoma is a rare bone cancer that develops in bones or soft tissue close to bones. It can grow anyplace in the body, but normally affects the arms, legs, spinal column, pelvis and ribs. Ewing sarcoma mainly affects kids and young adults. To survive this condition a DNA repair is required. Recently, a team of investigators revealed two drugs that interfere that collectively very successfully kill the Ewing Sarcoma cancer cells in laboratory cultures and mice.
The team reported their findings in the journal Oncotarget
Ewing sarcoma tumors generally develop in the hip bones, the ribs, or in the midsection of long bones, like the legs or arms. It can also develop in the spine and soft tissue close to the bone.
Most Ewing tumors are identified in teens, but they can also impact kids and young adults in their 20’s and 30’s. Every year in the US, about 250 kids and teenagers are identified with a Ewing tumor, the majority of which will be Ewing sarcoma of bone.
The 5-year survival rate for patients with a Ewing tumor that has not spread is around 70%. If the tumor has spread (generally it is called metastatic stage) when the condition is identified, the survival falls to below 2 and a half years.
The very frequent mutation that leads to Ewing sarcoma includes two genes – EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. These modifications take place during a person’s life-time and are only present in tumor cells. They are not inherited.
The new research develops on earlier research that recommended some kinds of Ewing sarcoma could be especially vulnerable to a group of medicines known as PARP inhibitors, if used together with DNA damage repair agents.
Olaparib and Trabectedin combination was ‘extremely synergistic’
Cancer cells, like healthy cells depend on DNA repair to sustain their genetic integrity to be able to multiply and propagate. There are a variety of cellular functions that perform DNA repair. One such process depends on a family of proteins known as PARP.
However, many cancers accept PARP as the DNA repair mechanism, which is why PARP inhibitors were formulated to treat cancer. One type of PARP inhibitor is a drug known as Olaparib – one of the medicines that the study looks into. Olaparib prevents the action of PARP1, a gene that activates DNA repair when damage is found.
The other drug used in this research is Trabectedin, which is also used as an anti-tumor drug. It works by producing breaks and irregular DNA structure in cancer cells, which in turn leads to cell death.
The investigators examined the result of the two drugs collectively on Ewing sarcoma. They performed two sets of tests -in vitro and in vivo.
In their research paper, they explained how the “combo of Olaparib and Trabectedin was identified to be highly synergistic.” It restricted cell growth and triggered cell death. In the mice, the tumors showed complete regression.
Enrique de Alava, Senior author of the study concludes:
“Our outcomes show that the combination of Trabectedin and Olaparib could possibly be a new therapeutic approach that should be researched in greater depth so that it can benefit people with Ewing sarcoma in the coming future.”