Advancements in Sarcoma Research and Treatment: Insights from Sarcoma Expert Nam Bui, MD

Soft tissue sarcomas (STS) are a type of cancer originating from soft tissues, such as muscles, fat, nerves, and blood vessels. They are primarily located within the connective tissues of the body. STS consist of a wide range of subtypes, with over 50 different recognized forms, each displaying unique characteristics and behaviors. These subtypes include liposarcoma, leiomyosarcoma, synovial sarcoma, and rhabdomyosarcoma. Despite the variety of subtypes, STS are a relatively rare orphan disease, accounting for less than 1% of all cancer diagnoses. The rarity of these tumors highlights the importance of specialized expertise and comprehensive treatment approaches to effectively manage and combat these challenging diseases.

We spoke with Stanford Cancer Institute member? Nam Bui , MD, a clinical assistant professor of medicine and sarcoma specialist, to gain further insights during Sarcoma Awareness Month.

Why are soft tissue sarcomas challenging to treat?

STS are challenging to treat because they are relatively rare and also heterogeneous. While STS fall under one specialty, it originates from many different organ types, leading to distinct behaviors and responses to treatments for each tumor type. Because each subtype has a unique natural history—meaning where it starts, how fast it grows, and how it responds to treatment—it is more accurate to describe them as a family of related diseases rather than as a single disease.?

Gaining a comprehensive understanding of the different types of STS and determining the most effective treatment approaches necessitates significant clinical expertise. For instance, a primary leiomyosarcoma can present in diverse locations, such as the abdomen, uterus, or limbs, each requiring distinct multidisciplinary treatment planning strategies.

Another reason why STS are difficult to treat is that, for the most part, we still use the same chemotherapies to treat sarcoma that we did decades ago. Moreover, STS are often not as chemoresponsive as other tumor types. Clinical trials are the only way to advance cancer treatment by bringing novel therapeutics into the clinic. However, due to the rarity of the disease, fewer patients are eligible to participate in clinical trials. Consequently, conducting large-scale trials to find novel agents or treatment strategies can be challenging.

How has sarcoma research evolved?

We are now subdividing these rare STS types and trying to treat them as individual entities instead of treating them as a whole with the same chemotherapy. We’re researching the genetic vulnerabilities specific to each distinct type of sarcoma, which allows us to develop improved treatment strategies.

There are new targets and an increased emphasis on precision medicine in sarcoma treatment.?Different types of cancer mutations may require specific therapies or interventions tailored to the individual’s unique genetic profile and sarcoma type. By looking at these mutations, we can exploit their biology and leverage them in cancer treatment by blocking the pathways tumor cells rely on for growth. This targeted approach holds promise for more effective and personalized sarcoma treatments.

Stanford has actively participated in nearly every significant sarcoma trial, leading to FDA approval of various drugs. We have witnessed long-term remissions in some of our patients who participated in these trials. It is important to acknowledge that not all trials have transformative outcomes, but there are instances where specific patients experience remarkable benefits.

One notable example is our?desmoid tumor trial , where participants reported a significant reduction in tumor size and pain. These participants were grappling with large sarcomas that caused immense discomfort, requiring them to rely on narcotics for pain management. However, the trial drug proved to be highly effective, significantly shrinking tumors and enabling participants to completely discontinue opioid use. As a result, they regained the ability to lead normal everyday lives.

How is precision medicine impacting treatment decisions??

At Stanford, we perform genetic sequencing on every sarcoma patient to ensure no targeted mutations are overlooked. Every day, we explore mutations to target. We know there are many mutations out there; however, we still lack the necessary drugs to address them all. That’s where the research comes in. We are pushing the envelope and actively working toward finding new drugs to apply to specific sarcoma mutations.

Immunotherapy is a revolutionary treatment that unleashes the body’s immune system to attack cancers. Unlike poisons, like chemotherapy, or targeting specific cancer mutations, immunotherapy activates the immune system to recognize tumors that have developed ways to hide from the immune system. Although it’s been approved in many tumor types, it is currently only available for one sarcoma type—alveolar soft part sarcoma, an extremely rare sarcoma subtype. We have conducted numerous immunotherapy trials; however, we have not observed the remarkable responses that we’ve seen in other tumor types. Consequently, we are now focusing on discovering specific sarcoma types that may exhibit greater responsiveness to immunotherapy, as well as determining whether blood draws can help determine immunotherapy effectiveness early on. Additionally, we are exploring combination strategies to enhance the effectiveness of attacking sarcomas. These combinations may involve combining immunotherapy with either chemotherapy or a targeted agent as we strive to optimize treatment outcomes for sarcoma patients.

Where do you see sarcoma research five to ten years from now??

I’m excited by the advancements in precision medicine and immunotherapy. I see the field steadily shifting towards targeted and precision medicine, especially immunotherapy, leveraging new ways of treating tumors instead of chemotherapy. We’ve seen patients with terminal diseases now living for years, with some achieving long-term remissions. For instance, I had a patient diagnosed with metastatic alveolar soft part sarcoma two and a half years ago, with widespread tumors throughout his lung. After receiving immunotherapy, he is now in complete remission, with CT scans showing no evidence of cancer. We are eagerly anticipating new therapies that will eradicate sarcoma and transform incurable diseases into chronic diseases or complete remissions.?

Is there anything else you’d like to underscore?

I would like to emphasize the importance of seeking consultations at major sarcoma centers, such as Stanford, for all sarcoma patients. These centers have a multidisciplinary team of experts specializing in surgery, radiation oncology, medical oncology, and pathology. Being academic-based, sarcoma centers handle a high volume of cases and have specialists dedicated to sarcoma treatment. Additionally, it is crucial for sarcoma patients to have the opportunity to have their cases presented at a sarcoma tumor board. Our tumor board meets virtually on a weekly basis, where rare tumor experts collaborate to identify the most effective cancer treatment and care strategy for each patient.

Lastly, sarcoma patients should be encouraged to enroll in clinical trials. While precision medicine and immunotherapy hold great potential, their effectiveness in treating sarcoma can only be validated through rigorous clinical trials. By enrolling in these trials, patients contribute to the exploration of the most effective strategies for sarcoma treatment. It is essential to test these strategies to determine their efficacy. Currently, we have several?actively accruing trials ?at Stanford.

By Sarah Pelta

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