Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>High-Grade Serous Ovarian Cancer (HGSOC) is the most fatal of gynecological cancers. The recurrence rate of HGSOC after treatment is more than 80%. The available treatment options for HGSOC are limited; standard of care includes surgery combined with chemotherapy, with radiation therapy in some advanced cases. Both chemotherapy and radiation therapy are known to induce tumor cell aggressiveness. Many cancer studies have demonstrated that cancer stem cells (CSCs) and the epithelial-mesenchymal transition (EMT) promote cancer aggressiveness, invasion, metastasis, and drug resistance. Therefore, to better understand the cause of the poor prognosis in HGSOC, our objective is to scrutinize the role of CSCs and EMT in chemo- and radiation resistance. To lead our inquiry, we utilized the SORE6 reporter to identify Sox2/Oct4 expression, which indicates the stemness, and the Zeb1 3’ UTR reporter to detect EMT. Using flow cytometry, we quantified the reporter activity in 10 ovarian cancer cell types, including chemo-sensitive and chemo-resistant ones, considering both cell lines and patient-derived cells. Chemo-resistant cells are grown under cisplatin treatment. We exposed some of these ovarian cancer cell lines to 0, 1, 2, 4 and 8Gy of 250 MeV proton and 6 MeV photon beams, then analyzed the reporter activity 72 hours post-radiation. Our findings exhibit that chemo-resistant cells express higher stemness and EMT levels than chemo-sensitive cells and have higher resistance to radiation. These reporters can detect radiation-induced stemness and EMT. Furthermore, stemness and EMT levels positively correlate with the radiation dosage increment. We conclude that these reporters are an efficient surrogate for detection of stemness and EMT and can be used to test strategies for prevention of therapy-induced aggressive phenotypes.</jats:p>
<jats:p>Citation Format: Yeonkyu Jung, Aaron Keniston, Ashley Antonissen, Ann Morcos, Antonella Bertucci, Marcelo Vazquez, Juli Unternaehrer. High grade serous ovarian cancer: Detecting stemness and EMT levels in response to chemo and radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1089.</jats:p>