Opdivo (nivolumab)

This overview provides a concise synthesis of targeted therapies under investigation or already in clinical use, including monoclonal antibodies against epidermal growth factor receptor (EGFR) (e.g., cetuximab) and immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab), as well as inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) or agents targeting angiogenic and intracellular signaling pathways such as VEGF and mTOR...Metformin and statins, for instance, have demonstrated anti-proliferative and pro-apoptotic effects in preclinical OSCC models. Notably, recent evidence suggests that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, may improve survival specifically in patients with PIK3CA-altered Head and Neck tumors, potentially through modulation of the COX-2/PGE2 axis. Although prospective evidence remains limited and somewhat heterogeneous, existing preclinical and observational studies suggest that these agents may improve survival and reduce treatment-related toxicity, further pointing to the relevance of molecular stratification in guiding future repurposing strategies. This article aims to map the current therapeutic landscape, highlighting both established molecular targets and emerging repositioned drugs in the management of OSCC and OPSCC.

The sequences for the anti-PD1 modules were derived from the clinical antibody nivolumab...Critically, in a serial rechallenge assay designed to simulate chronic antigen exposure, both armored CAR-T cell groups showed markedly enhanced proliferation and persistence compared to conventional CAR-T cells, which failed to expand after repeated stimulation. Our findings validate the bidirectional EF1 promoter as an efficient system for generating multi-functional T cells and demonstrate that armoring CAR-T cells with secreted anti-PD1 antibodies is a potent strategy to enhance their persistence and anti-tumor efficacy.

The observed toxicity was consistent with the known toxicity profile of immunotherapy and did not lead to discontinuation of therapy. Our case report highlights the need to test for predictive markers in patients with locoregionally advanced rectal cancer in order to identify specific subtypes of the disease that can be treated with immunotherapy with a high probability of achieving clinical complete remission, thereby avoiding potentially risky surgery.

In terms of OS, pembrolizumab + chemotherapy + canakinumab (Pembro-chemo-canakinumab) (SUCRA =0.90) showed great potential in improving outcomes, although its long-term efficacy still needed to be validated...For squamous patients, nivolumab + ipilimumab ± chemotherapy (Nivo-ipi-chemo) led in OS, while serplulimab + chemotherapy in PFS. First-line personalized treatment for PD-L1 <1%, advanced NSCLC should be histology-based, balancing efficacy and toxicity. Pembro-chemo and nivolumab + chemotherapy + bevacizumab combinations are recommended as the optimal first-line options for non-squamous patients, and Nivo-ipi-chemo for squamous patients.

The integration of checkpoint inhibitors with targeted immunomodulation and personalized therapeutic approaches may improve treatment efficacy. Future research should focus on refining patient selection criteria, enhancing macrophage-targeted therapies, and optimizing immune profiling techniques to maximize therapeutic outcomes for uterine leiomyosarcoma.

In the randomized SCANDIUM II trial, patients with metastatic UM received a one-time treatment with isolated hepatic perfusion using high-dose melphalan in combination with systemic immune checkpoint inhibition with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Patients with undetectable ctDNA 2-4 months after the start of treatment had significantly improved progression-free survival (P = 0.024), and a non-significant improvement in overall survival. In patients with UM liver metastases treated with combined hepatic perfusion and immune checkpoint inhibition, ctDNA may serve as a predictive biomarker and warrants further validation.

Patients with NSCLC and low TPS/high IC scores may benefit more from Nivo+Ipi than from Pembro due to distinct genomic and immunological features, including high TMB and Treg fraction.

P1/2, N=8, Active, not recruiting, University of Colorado, Denver | Trial primary completion date: Oct 2025 --> Aug 2026

P3, N=192, Recruiting, University of Kansas Medical Center | Not yet recruiting --> Recruiting

This is the first published case suggesting a potential role for leukotriene receptor antagonists in CYSLTR2-mutant UM. These findings support further preclinical and clinical investigation of montelukast as a repurposed therapy in this challenging disease entity.

P1, N=31, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Oct 2025 --> Jan 2026

P1, N=14, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting