Sarcomas: Unique Cancers that Merit Further Attention and Research

Sarcomas are unique compared to other types of cancer variations. In contrast to carcinomas, which arise from epithelial cells and account for 80-90% of cancers, the rarer sarcomas arise from the connective tissues of our body, including muscle, fat, bone, and cartilage.

Among adults in the United States, sarcomas account for one percent of all cancer diagnoses. The most common variation globally is Kaposi’s sarcoma, a cancer that forms in blood and lymph vessel lining, which was diagnosed in approximately 42,000 people in 2018. Unfortunately, sarcoma is more prevalent among children, representing 15% of childhood cancer diagnoses. Bone sarcomas in particular occur with greater frequency among children.

Numerous patients treated with conventional therapies like chemotherapy and radiation will eventually develop advanced sarcomas that have grown resistant to these approaches. Checkpoint inhibitor immunotherapies aren’t yet effective for most sarcoma patients either, and thus there is an unmet need for better options for patients, both to treat sarcoma and prevent its recurrence.

Immunotherapy could be that solution.

CRI has been funding research for immunotherapy treatments in all types of sarcomas for decades. Since 1997, more than $2.6 million of our funding has been allocated towards sarcoma research. This research covers sarcoma’s potential vulnerabilities to immunotherapy, targeting fusion-derived neoantigens in soft tissue sarcoma, and T cell receptor targets for chordoma, a form of sarcoma that affects the spine or the base of the skull. Four years ago, CRI and the Chordoma Foundation forged a research partnership to accelerate treatment options.

CRI Impact in Sarcoma, especially Chordoma via the CRI-Chordoma Foundation CLIP partnership

• Cassian Yee, MD, a CRI-Chordoma Foundation CLIP Investigator at the University of Texas MD Anderson Cancer Center, spoke with Arthur Brodsky, PhD, CRI’s associate director of scientific communications, about how he’s tackling chordoma.
• CRI-Chordoma Foundation CLIP Investigator Christopher Alvarez-Breckenridge, MD, PhD, at the University of Texas MD Anderson Cancer Center, is conducting research on chordoma’s potential vulnerabilities to immunotherapy.

• CRI-Chordoma Foundation CLIP Investigator Jean Paul Wolinsky, MD, at Northwestern University, is working to identify how malignant chordoma suppresses the immune system.

• CRI-Bristol Myers Squibb Postdoctoral Fellow Lauren B. Banks, PhD, at Memorial Sloan Kettering Cancer Center, focuses on cell therapies for sarcoma.

• CRI-Chordoma Foundation CLIP Investigator Judith Bovee, MD, PhD, of Leiden University Medical Center in the Netherlands, is researching immunity in chordomas for tailored immunotherapy.

• CRI-Chordoma Foundation CLIP Investigator Qilin Zhang, MD, of Huashan Hospital at Fudan University in Shanghai, is working on data-centric immunotherapy guides in skull base chordoma.
• CRI CLIP Investigator Aurelie Dutour, PhD, at Centre Léon BERARD in Paris, is working towards deciphering chordoma’s response to the immune system to aid the development of tailored immunotherapies.

Currently, there are three FDA-approved immunotherapy options for sarcoma patients, all of which are PD-1/PD-L1 checkpoint inhibitor immunotherapies. Atezolizumab is available for patients with alveolar soft part sarcoma, whereas dostarlimab and pembrolizumab are approved for patients with any type of advanced sarcoma that has genomic instability, such as DNA mismatch repair deficiency, high tumor mutational burden (TMB-high), or high microsatellite instability (MSI-high). With continuing support for sarcoma research and immunotherapy treatments, CRI hopes to eliminate sarcoma as part of our effort to create a world immune to cancer.