FOLR1 overexpression

Mirvetuximab soravtansine-gynx, an FRα-targeting ADC, has been approved by the FDA and EMA for the treatment of FRα-positive, platinum-resistant ovarian cancer... These findings highlight the critical importance of standardized, validated assays for FRα detection to ensure accurate patient selection for targeted therapies. The study emphasizes the need for further optimization of alternative antibodies before clinical implementation.

Estimated human dosimetry showed high absorbed dose for tumor and minimal absorbed dose for healthy tissues establishing its safety. In totality, FOLR1-targeted 225 Ac alpha-particle therapy is an efficacious and safe treatment with high feasibility for clinical translation to fight against ovarian cancer.

A positive correlation between HER2 and FOLR1 overexpression may be seen in high-grade endometrial carcinomas with aberrant p53 expression, which may extend to intratumoral heterogeneity of biomarker expression.

The optimized Folate-LT qPCR method provides a sensitive and specific approach for detecting FR-positive CTCs in gastric cancer. This technique addresses limitations of existing CTC detection methods by combining negative depletion with specific ligand targeting, requiring minimal blood volume, and avoiding size-based or epithelial marker-dependent limitations, and shows promise for early cancer detection, disease progression monitoring, and treatment response assessment, potentially improving clinical outcomes for gastric cancer patients.

We revealed that FOLR1 orchestrates the malignant advancement of GBM by stimulating the SRC/ERK1/2 signaling axis, underscoring its pivotal role in the pathogenesis of GBM.

Recently, the FDA approved mirvetuximab soravtansine for platinum-resistant ovarian carcinoma with FOLR1 overexpression, typically high-grade serous carcinoma... To our knowledge, this is the largest study to date of FOLR1 expression in USC. Nearly 1 in 5 USC patients are FOLR1+, independent of HER2 status. Further research testing the efficacy of FOLR1-targeted therapy in USC is needed, as approval could potentially double the proportion of patients with available targeted therapies.

Our results showed overexpression of FOLR1 and TROP2 in a significant proportion of high-grade EC, suggesting that targeted therapy against these markers may be a novel option for patients with EC. FOLR1 and HER2 positivity appeared mutually exclusive, while co-expression of FOLR1-TROP2 and HER2-TROP2 was also infrequent, observed in <5% of all tumors.

Together, these data showed that the assay is highly reliable, consistently producing evaluable results in the clinical setting. The VENTANA FOLR1 Assay is a robust and reproducible assay for detecting FRα expression and identifying a patient population that derived clinically meaningful benefit from MIRV in the SORAYA study.

Furthermore, blocking the interaction between epidermal growth factor receptor (EGFR) and the EGFR/AKT/glycogen synthase (GSK)3β signaling axis both abolished FOLR1's effects on the expression and nuclear aggregation of β-catenin. In summary, our work reveals a novel mode in which FOLR1 promotes the proliferation and migration of LSCC by enhancing the stability and nuclear translocation of β-catenin through the EGFR/AKT/GSK3β axis.

A number of methods have been developed to target FOLR1 in cancer therapy, including the development of FOLR1-targeted imaging agents for cancer diagnosis and the use of folate conjugates to deliver cytotoxic agents to cancer cells that overexpress FOLR1. Therefore, we focus on the most recent developments in employing FOLR1 for cancer diagnosis and treatment in this review, particularly with regard to cancers that affect women.

A 2nd generation FOLR1-CAR T cell was created by fusing the ScFv from farletuzumab (anti-FOLR1 monoclonal antibody) with a 4-1BB costimulatory and CD3z cytotoxicity domain... FOLR1-CAR T cells appear to have in vivo activity against U2OS cell line and support further testing of safety and feasibility in an early phase clinical trial for relapsed/refractory OS. >

The results are paired with in vitro reconstitution-based assays to map the numbers and characteristics of CAR:FOLR1 binding events to T cell activation. By generating a more complete mechanistic understanding of engineered cell-tumor cell interactions, we expect to generate actionable insights for the development of more effective cancer immunotherapies.