Sarcoma Cellular Therapeutics Initiative

Making Something New

Obligatory—this is not medical advice

Frequently, for our patients with sarcoma, therapies are not specifically designed for their disease, but rather for more common types of cancer. These medications are then trialed in sarcoma—with good intentions. For instance, let ‘s review cabozantinib, a tyrosine kinase inhibitor.¹ This is an agent initially studied in clear cell renal carcinoma, and later hepatocellular carcinoma.²³ During ASCO 2023, a large proportion of studies for patients with sarcomas evaluated the efficacy of cabozantinib either alone or in combination for varied histologic subtypes of sarcoma. ⁴⁵⁶ There is a rationale for why this medication would work. Tyrosine kinases have had broad efficacy by progression free survival before.⁷ Nonetheless, cabozantinib was not made with sarcoma in mind and so efficacy may be in a way serendipitous.

While I will never argue against appropriately designed clinical trials, this pathway has not led to much success in aggregate for our patients. Within the last 10 years there have been approximately a dozen FDA approvals that only account for the minority of patients with these disease states.⁸ There are many reasons why this is the case, particularly that the rate of accumulation of trials is directly proportional to the number of patients multiplied by time. Our incidence is much less than more common cancers, even when one combines all the diagnoses that fall within the soft tissue or bone sarcoma groupings.

At the University of California San Francisco, we have been tremendously fortunate. We are poised to utilize the clinical and laboratory expertise of dedicated scientists interested in shifting the modern paradigm of therapy for individuals with sarcomas, and other diseases. Dr. Kole Roybal and Dr. Gregory Allen have embarked on a journey to harness the power of targeted cellular therapy products against sarcomas. They have a tremendous experience in the area, with publications in high impact journals.⁹¹⁰¹¹ Now, we are just beginning our journey, and there is much work to be done. Nonetheless, we are very enthusiastic about the prospect of building treatments specifically for sarcomas. As an example, osteosarcoma, which has a median age at diagnosis of 12, unfortunately has been without significant advances for the last 3 decades. Our hope is to be able to change this.

Combining our shared expertise, we will assiduously labor to build, and subsequently test unique, cellular therapies utilizing modern techniques. These will be developed from the ground up to target rare diseases. Furthermore, by manufacturing, and evaluating these agents on the same campus, we will be able to iterate and improve at a rate and scale never previously done for sarcoma treatments. It is our sincerest aspiration to create new and effective therapies and I believe that we have the tools here at UCSF to do so.

If you’re curious to read more about this program, read UCSF’s announcement here.

1. https://www.fda.gov/drugs/resources-information-approved-drugs/cabozantinib-cabometyx

2. https://pubmed.ncbi.nlm.nih.gov/27279544/

3. https://pubmed.ncbi.nlm.nih.gov/29972759/

4. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.11503

5. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.17_suppl.LBA11504

6. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.11505

7. https://pubmed.ncbi.nlm.nih.gov/22595799/

8. https://www.cancer.gov/about-cancer/treatment/drugs/soft-tissue-sarcoma

9. https://www.science.org/doi/abs/10.1126/science.aba1624

10. https://pubmed.ncbi.nlm.nih.gov/36520914/

11. https://pubmed.ncbi.nlm.nih.gov/29590036/