Like other cancers, tumor cells in Ewing sarcoma – a rare bone cancer that primarily affects children and young adults – have to keep repairing their faulty DNA to survive. Now, a team of researchers shows two drugs that interfere with this process work together very effectively to kill the cancer cells in lab cultures and mice.

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The researchers found that the drug combination inhibited cell proliferation and facilitated cell death in lab cultures of Ewing sarcoma cancer cells and mice with tumors.

The team – including members from the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona, Spain – describes the finding in the journal Oncotarget.

Ewing sarcoma tumors usually grow in the hip bones, the ribs, or in the middle of long bones, such as the legs or arms. It can also grow in the spine and soft tissue around the bone.

Most Ewing tumors are diagnosed in teenagers, but they can also affect children and young adults in their 20s and 30s. Each year in the US, around 250 children and teenagers are diagnosed with a Ewing tumor – most of which will be Ewing sarcoma of bone.

The 5-year survival rate for people with a Ewing tumor that has not spread is about 70%. If the tumor has spread (metastasized) when the disease is diagnosed, the 5-year survival drops to less than half of this.

The most common mutation that causes Ewing sarcoma involves two genes – the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. These changes occur during a person’s lifetime and are only present in tumor cells. They are not inherited.

The new study builds on previous research that suggested some types of Ewing sarcoma could be particularly sensitive to a group of drugs called PARP inhibitors, if used in combination with DNA damage repair agents.

Cancer cells – like healthy cells – rely on DNA repair to maintain their genetic integrity in order to multiply and spread. There are a number of cellular processes that carry out DNA repair. One such process relies on a family of proteins called PARP.

However, many cancers favor PARP as the DNA repair mechanism, which is why PARP inhibitors were developed to treat cancer. One type of PARP inhibitor is a drug called Olaparib – one of the drugs that the study investigates.

Olaparib blocks the action of PARP1, a gene that triggers DNA repair when damage is detected.

The other drug the study investigates – Trabectedin – is also used as an anti-tumor treatment. It works by causing breaks and abnormal DNA structure in cancer cells, which in turn triggers cell death.

The researchers tested the effect of the two drugs together on Ewing sarcoma. They ran two sets of tests – one on cancer cells (in vitro) and the other on mice implanted with grafts of human Ewing sarcoma tumors (in vivo).

In their study paper, they note how the “combination of Olaparib and Trabectedin was found to be highly synergistic.” It inhibited cell proliferation and facilitated cell death. In the mice, the tumors showed complete regression.

Senior author Enrique de Alava, of the Instituto de Biomedicina de Sevilla (IBiS) and the Virgen del Rocio Hospital in Seville, concludes:

Our results demonstrate that the combination of Trabectedin and Olaparib could be a new therapeutic strategy that should be studied in greater depth so that it can benefit patients with this disease in the near future.”

In February 2014, Medical News Today also learned about an earlier international study led by IDIBELL that suggested a treatment option for metastatic Ewing sarcoma might be found in switching off the gene SIRT1, which codes for the protein Sirtuin1.

In that study, the team showed that overexpression of Sirtuin1 was very significantly linked to metastasis in samples from patients with Ewing sarcoma.