The Future of Sarcoma: Nanotechnology, Immunotherapy, and Shark Research

H. Thomas Temple, MD

While much of what is on the horizon in sarcoma is not widely known, there are several exciting advancements in the pipeline, says H. Thomas Temple, MD, senior vice president for Translational Research and Economic Development, professor of Orthopedic Surgery at Nova Southeastern University, and chief medical officer of Vivex Biomedical.

Numerous diagnostic advancements are being investigated, including the use of image-guided resection to improve surgical procedures and using tumor-marker antigens to better determine ideal targeted therapies for patients with sarcoma, says Temple.

At Nova Southeastern University, researchers are even investigating marine life in connection with sarcoma research, in an effort to understand what causes tumorigenesis and perhaps more importantly, what inhibits tumor growth.

Regarding treatment, researchers are making progress on understanding the potential of nanotechnology platforms for the treatment of sarcoma, as well as exploiting inhibitors to molecules such, as PD-L1. Advancements in high-dose rate brachytherapy also have potential to significantly improve outcomes for patients with sarcoma, says Temple.

“I think these new advancements are a great start,” says Temple. “They are not the holy grail, but they are certainly a bridge to a greater understanding and better diagnostic tools and therapeutics for this rare and very heterogeneous disease.”

OncLive: What diagnostic advancements do you see on the horizon in sarcoma?

In an interview with OncLive, Temple explains where he sees the future of sarcoma going and what diagnostic technologies and therapeutic advancements he is most excited about.Temple: I think one of the most exciting new technologies is image-guided resection. This fuses magnetic resonance (MR) data with real-time ultrasound imaging. A robotics platform can be developed based on echogeneic image feedback. This allows a surgeon to map normal structures and guide tumor resection. This has real potential in modern surgical therapeutics.

Is Nova Southeastern University currently involved in any diagnostic research?

In addition, discovery and quantitative measurement of tumor marker antigens show significant potential. This process allows us to look at numerous immunohistochemical markers and assess tumor heterogeneity. Using bioinformatics based on the expression of certain markers, we might be able to find gene pathways and work backward to determine potential targeted therapies. This technology has been around, but it has not been truly exploited. Genomics is one of the areas that we are especially interested in, as well.One really exciting development is the GWATCH Cyber Suite, which was developed by Dr. Steve O’Brien here at Nova Southeastern University in conjunction with his colleagues at the Saint Petersburg State University in Russia.

This looks at a tumor’s entire genomic code for outliers: genes that are over-expressed. This program displays real data on a virtual chromosome highway. It is really cool.

Using the technology, we can look at gene expression that is visualized three-dimensionally. We can look at abnormal genes that are being expressed, hone in on them, working backwards we can attempt to develop targeted therapies. This is an area of sarcoma research that we are investing in heavily. It is really a beautiful graphic description of what is going on within the cancer cell genome.

What treatment advances are you most excited about in sarcoma?

In conjunction with our oceanographic college, we are also investigating invertebrates and vertebrates to identify certain species that do not develop cancers or do so at very low rates; for example, the shark species. It is very rare to find tumors in sharks. By looking at that genome we may be able to identify certain pathways that lead to tumor suppression. This is research that is very out there, and probably not on the near horizon, but it is very interesting.One area that I am really excited about is the potential of targeted radiotherapy, nanoknife. Standard external beam radiotherapy takes 6 weeks and has several downsides, including radiation dermatitis, fibrosis and the possibility of causing a secondary sarcoma. Nanoknife can be used in conjunction with a radiopaque matrix. The procedure involves tumor resection and placement of this radiopaque matrix in the tumor bed, that resorbs over time. When the wound is closed you sort of a have a 3D-visualization of where the tumor was.

Then you can employee targeted radiotherapy over a much smaller area and just treat the periphery of that whole field. Another iteration is a biologic matrix that is preloaded with a radiotherapeutic source. I think that is very exciting. We actually published this concept when I was at the University of Miami and it didn’t really take off because most insurance companies were not willing to reimburse this type of therapy. I think it is something on the horizon for smaller, deep-seated tumors.

Another area that I am excited about and that we have worked very hard to develop is high-dose rate brachytherapy. It is not a new concept; it has been around for a long time. It allows you to consolidate adjuvant treatment for patients with sarcoma in a short period of time. We’ve demonstrated equivalency with external beam radiation.

Do you see potential for immunotherapy in sarcoma?

There are fewer long-term side effects. It is delivering exceptionally high doses of radiotherapy in an area where the patients needs it most—the closest margin. This has considerable up-side for these patients. They are able to get back to work quicker, it has reduced their time in therapy, and has really demonstrated better long-term outcomes with regard to soft tissue fibrosis, lymphedema and joint stiffness.We are looking at PD-L1 synced with targeted molecules to improve immune t-cell response. PD-L1 is really big right now, but nobody has really looked at it in sarcomas. We’ve been able to look at 3D-cultures of different sarcoma lines and investigate stromal (normal) host cell influences on tumor growth. These observations have lead to evaluating different targeted interventions with or with stromal cells and how tumors respond to these types of interventions.

I think that having these kinds of technologies that allow you to look at biologic activity and cell-cell interactions in 3D-cultures may even someday take the place of early phase 1 trials. You can actually take a tumor, expand it, and isolate it and look at it in relationship to different supporting cells and then investigate different agents and drugs that you are anticipating using in a clinical trial and measure in a very accurate way how the tumor responds.