Sarcoma Expert Shares Excitement Over New Targets and Treatments

Brian A. Van Tine, MD, PhD

With novel treatments advancing through the pipeline and new metabolic targets being discovered, oncologists can expect the field of sarcoma to evolve dramatically over the next few years, according to Brian A. Van Tine, MD, PhD.

“All of the new drugs coming into sarcoma right now really make this a field that is maturing very rapidly,” explains Van Tine. “There are so many opportunities for drug development; this is just kind of a fun field to be in right now.”

Van Tine is involved in ongoing research examining the deficiency of argininosuccinate synthetase 1 (ASS1) in synovial sarcoma cells with the use of global metabolic approaches. The work has led to the identification of the first dual metabolic therapy using an arginine deiminase and a glutaminase inhibitor.

OncLive: Can you discuss your study on the discovery of metabolic targets?

Van Tine, assistant professor of Medicine, director of the Sarcoma Program, Division of Medical Oncology, Siteman Cancer Center, University of Washington School of Medicine in St. Louis, discussed his research with OncLive at the 2015 Connective Tissue Oncology Society (CTOS) Annual Meeting. In the interview, Van Tine also provides insight on the impact existing drugs are making on the treatment landscape and what community oncologists need to know about this ever-changing field.Van Tine: This is really exciting. We actually spent a lot of time over the last couple of years dissecting the metabolic properties of synovial sarcomas. We’ve actually dissected to a point where we have 2 metabolic targets.

We discovered a brand new metabolic deficiency in synovial sarcoma just by studying properties of glucose and glutamine. We dissected down and found this wonderfully silenced gene that completely alters with how glucose and glutamine go in the cells, and it became druggable—which really became kind of fun.

What is the importance of understanding basic science in sarcomas?

What is some other exciting research in the field you can share?

We really had a good time explaining the hardcore basic science that goes in sarcoma.It was discovered that we actually treat 173 different forms of sarcoma. If you begin, mechanistically, taking those apart, there are lots of different therapeutic drug options you can develop. We carry an orphan disease designation that really allows us to take rare tumors and therapies that are successful for small groups of people but then allow pharmaceutical companies to come in and exploit these drugs.One of the most exciting things, other than olaratumab, evofosfamide, trabectedin, eribulin, and all our big drugs, may be in the work of Dr Brian Rubin. This actually shows a novel specific genetic translocation in epithelioid hemangioendothelioma, and it potentially can be druggable.

What can you say about the therapeutic advancements we have had?

Focusing in this area, he may have—through very careful, meticulous work in the Cleveland Clinic—really come upon, essentially, a transformative therapy or 2 for a disease that is really underserved.Trabectedin and eribulin are agents where 1 of which showed a progression-free survival benefit and the other showed an overall survival benefit. These are new drugs for which sarcoma doctors are going to really have to begin educating and working with our community partners. These are drugs that we are not only going to be using a lot, but are going to work.

What are the next steps you envision taking place in this field?

What should community oncologists know about where this field is going?

With that type of positivity, it is really kind of an exciting time to be here.The highlights that are coming in the near future are all of the combinations we are going to be able to use, all of the [investigation] that is coming in to figure out what agent goes with what, which patients should receive these combinations, and the timing of when patients should get them. There is going to be a lot of work in this field, especially in the next couple of years.I still believe that the standard of care is going to remain in clinical trials, and keeping the patients involved in as many clinical trials as possible is what we need to focus on.