E7820

This study uncovered that ITGA2 drives osteosarcoma progression and aggravates osteolysis via the "ITGA2-osteoclast axis", with high expression predicting poor outcomes. Mechanistically, ITGA2 promoted tumor invasion and bone metabolism imbalance by regulating osteoclastogenic signaling, while its targeted inhibition synergistically suppresses tumor growth and restores bone homeostasis, highlighting ITGA2 as a pivotal therapeutic target for osteosarcoma.

Our findings showed that ITGA2 is overexpressed in K562R cells and ITGA2 inhibitor E7820 (2.5 µM) treatment significantly decreased cell viability and induced apoptosis in both sensitive and resistant cells. Flow cytometry confirmed ITGA2 inhibition at the protein level, and rhodamine assays revealed reduced MDR1 activity in treated cells. These results demonstrate that targeting ITGA2 may overcome imatinib resistance and offer a novel therapeutic strategy for CML.

The global incidence of primary liver cancer ranks sixth among malignant tumors, while its mortality rate ranks third and is the second leading cause of cancer-related deaths in China [...].

P2, N=12, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

Importantly, our results reveal that the pharmacological depletion of RBM39 by using the anti-cancer aryl sulfonamide (E7820), a drug known for its oral bioavailability and safe administration, effectively represses osteosarcoma growth and sensitizes osteosarcoma cells to cisplatin treatment both in vitro and in vivo. Our findings unveil the crucial role of RBM39 in modulating tumor growth and cisplatin sensitivity in osteosarcoma cells, suggesting that the combination of aryl sulfonamides with cisplatin may benefit patients with osteosarcoma.

P2, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

E7820 and Indisulam (E7070) are sulfonamide molecular glues that modulate RNA splicing by degrading the splicing factor RBM39 via ternary complex formation with the E3 ligase adaptor DCAF15. Furthermore, E7820, in combination with olaparib, exerted a synergistic effect, and E7820 was even effective in an olaparib-resistant cell line. In conclusion, HRD is a promising predictive biomarker of E7820 efficacy and has a high potential to improve the prognosis of patients with HRD-positive cancers.

P1/2, N=5, Terminated, Eisai Inc. | Completed --> Terminated; The study was terminated early as the combination of E7820 and FOLFIRI was deemed to be not tolerable, hence no efficacy analysis was conducted.

Secondary endpoints include overall and event-free survival. Correlative biomarker and pharmacodynamic parameters will be assessed as exploratory endpoints including effects on RBM39 protein levels, changes in global and key target splicing events, and evaluation of DCAF15 mRNA levels and response to therapy.

P2, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Aug 2023 --> Aug 2024

P2, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=38 --> 12