Abstract 6224: The bad, the ugly and the ultra-rare: All cancers are equal in the face of personalized medicine
Authors: Loskutov Juergen , Regenbrecht Manuela , Sauer Rica , Finkler Sabine , Niethard Maya , Reinhard Christoph , Regenbrecht Christian 
Published: June 2022

Cancer represents a huge health problem worldwide and is well-recognized as an extremely heterogeneous disease affecting all the tissues and organs. The incidence of the particular cancer type is directly connected to the availability of specific medication and amount of the research focused on it, resulting in a high unmet medical need for treatment options for rare cancers. Currently, NCI defines “rare cancer” as cancer with an incidence rate below 15 per 10^5 people per year and recently the term “ultra-rare cancer” was defined as cancer with an incidence rate below 1 per 10^6 people per year. These encompass drastically understudied entities, usually with poor prognosis and grim outlook for an improvement in treatment. Low incidence of such cancers makes development of targeted therapies not interesting from a commercial point of view and completely abolishes the possibility of large-scale clinical trials. Therefore, a personalized medicine approach appears to be the most promising strategy for the patients to get adequate care.

Here we report our experience with personalized oncology solutions for rare and ultra-rare cancers. We utilized patient derived 3D (PD3D) cultures to evaluate prospective therapeutic options in these exceptional cases to support the oncologists in providing personalized care to the patients. Fresh surgical specimens underwent several steps of mechanical and chemical dissociation. Subsequently, cell aggregates were seeded into 24 well plates in matrix-like scaffolds and allowed to grow until they started forming colonies. After harvesting, the cells underwent pathology evaluation to confirm origin and diagnosis. Therapies, recommended by the case leading oncologist, were used for drug sensitivity testing after transferring cells semi- automatically to 384-well plates.

Over the last 18 months, we handled 6 cases classified as rare or ultra-rare cancers. The diagnoses included: clear cell sarcoma, extra-skeletal myxoid chondrosarcoma, CIC-rearranged round cell sarcoma, pleomorphic liposarcoma, cardiac angiosarcoma and clear cell endometrial carcinoma. In all cases we were able to successfully establish PD3D cultures and perform a drug screen, identifying a potential treatment for the patient.

Overall, our results indicate that it is feasible to utilize our testing strategy for rare and ultra-rare cancer entities. Further research and rigorous follow up is required to confirm the benefit of the personalized approach vs current strategies. However, a demand for personalized care in such cases is clearly visible.

Citation Format: Juergen Loskutov, Manuela Regenbrecht, Rica Sauer, Sabine Finkler, Maya Niethard, Christoph Reinhard, Christian Regenbrecht. The bad, the ugly and the ultra-rare: All cancers are equal in the face of personalized medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6224.