What’s New in Ewing Tumor Research and Treatment?

Research on Ewing tumors (Ewing sarcomas) is being done at many medical centers, university hospitals, and other institutions across the world.

Understanding and diagnosing Ewing tumors

Scientists are developing new techniques to more accurately diagnose Ewing tumors. New lab tests of tumor samples are being studied to see if they can help better identify Ewing tumors and give more information on how well treatments might work against that particular tumor.

As an example, advances in technology are now allowing doctors to do genomic testing, which looks at all of the genes inside the cancer cells, to better understand what makes these cells different from normal cells. Some of these differences might prove to be useful targets for developing new treatments for Ewing tumors (see below).

Treatment

Researchers are looking to develop better treatments for Ewing tumors, as well as to find less toxic treatments for those that can be cured.

Radiation therapy

Ewing tumors are very sensitive to radiation therapy, but because of its possible side effects, it's most often used only if surgery can't be done (or can't remove the entire tumor). Newer, more focused types of radiation therapy can help doctors treat tumors while lowering the dose of radiation to nearby healthy body tissues.

Chemotherapy

Doctors are studying new chemotherapy combinations, especially for Ewing tumors that come back (recur) after treatment. These combinations often include chemo drugs such as topotecan, irinotecan, temozolomide, gemcitabine, docetaxel, and mithramycin (plicamycin).

Doctors are also trying to make the currently used drugs more effective by changing the way they are given. For example, they have found that giving the standard VAC/IE (VDC/IE) chemo regimen more often – that is, every 2 weeks instead of every 3 weeks – seems to lower the chance of localized Ewing tumors coming back, without increasing the risk of serious side effects. This is often called compressed chemotherapy.

Researchers are also studying high-dose chemotherapy with stem cell transplants in those with Ewing tumors that are unlikely to be cured with current treatments.

Targeted drug therapy

As noted in What Causes Ewing Tumors?, great progress is being made in understanding the changes in genes and chromosomes that cause Ewing tumors to form.

This knowledge has already been used to develop very sensitive lab tests to detect this cancer, and doctors are now studying how to best use these tests to guide the choice of treatment. It might also lead to new drugs that target these changes in Ewing tumor cells.

Some new drugs that target specific changes in Ewing tumor cells are already being tested. For example, TK216 is a drug that targets the main fusion protein in Ewing tumor cells that is thought to help these cells grow. Early studies of this drug in people with Ewing tumors are now under way.

Also being studied in clinical trials are drugs that target the insulin-like growth factor receptor-1 (IGF-1R), a protein on some cancer cells that causes them to grow. Early studies have found that drugs like this, such as ganitumab, can shrink some Ewing tumors and slow down the growth of others. So far, this benefit has been temporary in most cases. These drugs may work best when combined with other drugs, which is now being tested.

Other drugs being studied for use against Ewing tumors include:

• Drugs that target certain proteins that help tumors grow and make new blood vessels, such as cabozantinib (Cabometyx) and regorafenib (Stivarga)
• Drugs that target the PARP protein, such as olaparib (Lynparza) and talazoparib (Talzenna)
• Drugs that affect which genes in a cell are active, such as vorinostat (Zolinza) and seclidemstat

Immune therapy

Another promising approach to treatment, known as immunotherapy, helps the body’s own immune system recognize and attack the tumor cells. Some newer types of immune therapies, such as immune checkpoint inhibitors and CAR T-cell therapies, have shown a great deal of promise in treating other types of cancer, and some of these approaches are now being looked at for Ewing tumors. These treatments are still in the early stages of testing at this time.