Patient-Specific Sarcoma Organoids for Personalized Translational Research: Unification of the Operating Room with Rare Cancer Research and Clinical Implications.
Ann Surg Oncol
; 29(12): 7354-7367, 2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-35780216
ABSTRACT
INTRODUCTION:
Sarcoma clinical outcomes have been stagnant for decades due to heterogeneity of primaries, lack of comprehensive preclinical models, and rarity of disease. We hypothesized that engineering hydrogel-based sarcoma organoids directly from the patient without xenogeneic extracellular matrices (ECMs) or growth factors is routinely feasible and allows rare tumors to remain viable as avatars for personalized research.METHODS:
Surgically resected sarcomas (angiosarcomas, leiomyosarcoma, gastrointestinal stromal tumor, liposarcoma, myxofibrosarcoma, dermatofibrosarcoma protuberans [DFSP], and pleiomorphic abdominal sarcoma) were dissociated and incorporated into a hyaluronic acid and collagen-based ECM hydrogel and screened for chemotherapy efficacy. A subset of organoids was enriched with a patient-matched immune system for screening of immunotherapy efficacy (iPTOs). Response to treatment was assessed using LIVE/DEAD staining and metabolic assays.RESULTS:
Sixteen sarcomas were biofabricated into three-dimensional (3D) patient-specific sarcoma organoids with a 100% success rate. Average time from organoid development to initiation of drug testing was 7 days. Enrichment of organoids with immune system components derived from either peripheral blood mononuclear cells or lymph node cells was performed in 10/16 (62.5%) patients; 4/12 (33%) organoids did not respond to chemotherapy, while response to immunotherapy was observed in 2/10 (20%) iPTOs.CONCLUSIONS:
A large subset of sarcoma organoids does not exhibit response to chemotherapy or immunotherapy, as currently seen in clinical practice. Routine development of sarcoma hydrogel-based organoids directly from the operating room is a feasible platform, allowing for such rare tumors to remain viable for personalized translational research.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
/
Neoplasias de Tecidos Moles
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article