Preclinical studies in soft tissue sarcomas may be tomorrow’s targeted therapies

Thursday, July 21, 2022

Author: Jianguo Huang, Ph.D., assistant member, Preclinical Cancer Therapy Laboratory, Earle A. Chiles Research Institute, Providence Cancer Institute


Sarcomas encompass a broad group of cancers that begin in the bones or the soft tissues of the body, such as muscles, joints, tendons and fat. This rare type of cancer affects children and adults. It can develop almost anywhere in the body, though it occurs most commonly in the arms, legs, head, neck and back.  

There are over 70 types of sarcomas. Some of the most common include:

Although the underlying cause of most sarcomas is not fully understood, we know that genetic and environmental factors play a role. However, research is limited, especially in studies related to soft tissue sarcomas. There currently isn’t a reliable preclinical research model, making it difficult for scientists to study genetic mutations and tumor metastases.

That’s why I chose this field as my research focus, with an emphasis on undifferentiated pleomorphic sarcoma (UPS), an especially difficult type of soft tissue sarcoma to treat. I’m fascinated by the complexity of soft tissue sarcomas and the opportunity to help improve therapies.

New lab focused on soft tissue sarcomas research
During my postdoctoral work at Duke University, I joined David Kirsch M.D., Ph.D., in his radiation oncology lab where I was introduced to sarcomas. I realized that this rare type of cancer posed a multifaceted puzzle to solve. Dr. Kirsch encouraged me to pursue my preclinical research using genetic screening approaches, such as CRISPR/Cas technology, to identify drivers of soft tissue sarcomas.

Because sarcomas are rare and genetically complex, developing clinical trials for patients poses a unique challenge that must be addressed in preclinical studies. Leading the Preclinical Cancer Therapy Laboratory at Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, I hope to fill a gap in soft tissue sarcomas research. Our team is studying the biology of sarcomas to help us better understand how to eliminate sarcoma cells at primary and metastatic sites.

Treatment options for soft tissue sarcomas currently include chemotherapy, radiation and surgery with some clinical trials showing encouraging results using immune checkpoint inhibitor agents in treating UPS. But it is unknown why a small group of patients responds to this type of immunotherapy while most patients don't respond.

In our preclinical studies, this is one of the challenges we hope to address, with the goal of establishing a mechanism for developing targeted therapies for UPS and other sarcomas.

Collaborating with Providence research colleagues
Earle A. Chiles Research Institute offers many opportunities to collaborate with multiple teams in studying potential new therapies. In addition to working with other researchers here to develop a specialized immune checkpoint inhibitor for UPS, I’m working with Eric Tran, Ph.D., and his Adoptive Cell Therapy Lab, helping to develop next-generation neoantigen T-cell receptor (TCR) therapy using CRISPR/Cas gene editing. This could be applicable for generating an adoptive cell therapy for UPS and other sarcomas.

Currently, there are two multi-indication clinical trials with sarcoma cohorts open at Providence Cancer Institute. As we develop preclinical models for soft tissue sarcomas, we hope to translate those findings into clinical trials specific to treating different types of sarcomas.

Enrolling and referring patients in clinical trials
At Providence Cancer Institute, new studies are added frequently to our clinical research portfolio:

Studies for many types of cancer and advanced cancers

Please contact our clinical research office to learn more or to refer a patient:

 

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