Ali Hmedat

Inhibition of RNA-binding proteins enhances immunotherapy in ovarian cancer

Abstract High-grade serous ovarian cancer (HGSC) accounts for more than 70% of ovarian cancer-related deaths, yet therapeutic progress remains stagnant. Among the four molecular subtypes reported for HGSC, the C5 subtype is distinguished by high proliferation and immune evasion with an unfavorable MHC-I/ PD-L1 ratio. However, the molecular drivers of this immune desert state remain largely undefined. Here, we identify RNA-binding proteins (RBPs) as key regulators of immune evasion in C5-HGSC through integrated single-cell and bulk RNA sequencing. We perform a targeted loss-of-function screen in C5-like cell models and find IGF2BP1 as a central mediator of immune evasion in vitro and in vivo. Mechanistically, IGF2BP1 abrogates interferon-gamma signaling by accelerating IRF1 protein degradation, thereby suppressing MHC-I presentation. We also discover that IGF2BP1 decouples PD-L1 expression from IRF1 -dependent transcription and reshapes the immune receptor landscape to limit immune cell infiltration and T cell activation. Therapeutically, the small-molecule BTYNB effectively inhibits IGF2BP1 and synergizes with PD-1 blockade to overcome immune evasion in vivo. Multi-spectral imaging confirms these findings in human HGSC tissues and highlights the role of oncofetal RBPs as molecular drivers of the C5-HGSC subtype. This subtype-wide survey uncovers a previously unrecognized RBP–interferon regulatory axis and establishes RBP inhibition as a therapeutic strategy to enhance immune checkpoint therapy in immunologically cold ovarian tumors.

The Therapeutic Potential of Laurus nobilis L. Leaves Ethanolic Extract in Cancer Therapy

This study explores the anticancer, antioxidant, and phytochemical activities of Laurus nobilis L. ethanolic leaf extract. The extract demonstrated selective cytotoxicity against four human cancer cell lines, showing strong cytotoxic effect against ovarian (ES2), head and neck (SAS), and colorectal (HT-29) cancer cells, with IC50 values ranging from 3.8 ± 0.3 to 4.4 ± 0.6 µg/mL. Notably, it exhibited only moderate inhibition of the MDA-MB-231 breast cancer cell line (IC50 = 18.5 ± 0.8 µg/mL), possibly reflecting intrinsic differences in cell line sensitivity. Importantly, the extract showed low toxicity toward normal human fibroblasts (HDF), with an IC50 value exceeding 100 µg/mL, indicating a favorable selectivity profile. The flow cytometry analysis showed that the extract caused cell death and stopped the cell cycle in both SAS and ES2 cancer cell lines. In SAS cells, extract treatment significantly increased apoptotic cells (21.1% ± 0.3%) compared to the control (6.3% ± 0.4%), along with G2 phase accumulation, indicating G2 arrest. Similarly, in ES2 cells, apoptosis increased (16.2% ± 1.3% vs. control 8.1% ± 1.0%), and a significant cell accumulation in the S phase was observed, suggesting disruption of cell cycle progression. Antioxidant screenings showed impressive dose-dependent DPPH radical scavenging activity (25–2000 µg/mL), although less potent than ascorbic acid (2.6 µg/mL). UPLC-QTOF/MS phytochemical analysis revealed various phenolic constituents, such as flavonoids and phenolic acids, and an inferred association with the recorded bioactivities. This preliminary work indicates that L. nobilis extracts may act as natural anticancer and antioxidant agents; however, it was limited to in vitro testing with non-standardized samples, underscoring the need for further research to validate and extend these findings for future applications.