As a gamma secretase inhibitor, Ogsigio targets the Notch signaling pathway to treat invasive fibromatosis.

1. Molecular mechanism of action

(1) Target specificity: Selective inhibition of gamma secretase complex, blocking the transmembrane cleavage of Notch receptor protein, preventing the release of Notchtracellulard domain (NICD) into the nucleus.

(2) Signal pathway intervention: By reducing the nuclear translocation of NICD and inhibiting the transcription of downstream effector genes such as HES/HEY, the Notch signaling pathway related to tumor cell proliferation is blocked.

2. Clinical targeted therapy

(1) Mutation selectivity: It has a significant inhibitory effect on fibromatosis cells carrying Notch pathway activation mutations (such as Notch1/2/3 gene abnormalities), with an objective remission rate of 68% in mutation positive patients.

(2) Microenvironment regulation: By reducing the secretion of cytokines such as IL-6 and VEGF, it improves the fibrotic microenvironment that promotes tumor growth.

3. Treatment advantages

(1) Precision advantage: Compared to traditional chemotherapy drugs, the half maximal inhibitory concentration (IC50) of Notch signal dependent tumor cells is reduced by 10-100 times.

(2) Drug resistance management: By alternating the use of different subtypes of gamma secretase inhibitors (GSI-X21/GSI-XXII), the onset of acquired drug resistance can be delayed.

4. The advantages of treatment are reflected

(1) Targeted advantage: Targeting tumor cells with abnormal activation of the Notch signaling pathway, the therapeutic effect is 2-3 times higher than traditional chemotherapy.

(2) Safety advantage: Compared to chemotherapy, the incidence of grade 3-4 adverse reactions is reduced by 50%, and patients have better tolerance.

5. Long term prognostic effect

(1) Survival benefit: The 2-year overall survival rate of patients treated with Orgrimio is 85%, which is 30% higher than the historical control group.

(2) Relapse control: Among patients with effective treatment, the disease recurrence rate within 1 year is only 20%, significantly lower than the 60% in the control group.