Structure-function drug screening of FDA-approved agents blocking IQGAP3-SOX2 binding identifies trimetrexate as a brain penetrant pharmacologic disruptor of IQGAP3 function in radioresistance, sensitizing GSCs to radiotherapy. These results identify molecular underpinnings for biomechanical promotion of cancer stem cell maintenance and therapeutic resistance, informing therapeutic strategies to augment efficacy of radiotherapy.

Traditional IT agents such as methotrexate or cytarabine were generally associated with modest survival outcomes, whereas more recent studies evaluating IT pemetrexed and molecularly guided regimens reported longer survival in selected cohorts, particularly in EGFR-mutant NSCLC-LM. Ommaya reservoir-based delivery may offer practical advantages for repeated treatment and CSF monitoring in appropriately selected patients, with acceptable toxicity and manageable device-related risks. Emerging data on pemetrexed-based intrathecal regimens and other molecularly informed approaches suggest potential benefit in selected subgroups, but prospective, multicenter, mutation-stratified studies are needed to refine patient selection, optimize dosing strategies, and define the comparative role of different intrathecal delivery routes.

The current standard of care for induction treatment is based on high-dose methotrexate as the central component, followed by consolidating high-dose chemotherapy and autologous stem cell transplantation in eligible patients...Given the significant prognostic and therapeutic implications of the immune microenvironment, its impact should be reflected and validated in future standard risk stratifications. Integrating validated immune biomarkers with emerging immunotherapeutic strategies has the potential not only to improve individual patient outcomes but also to optimize the overall structure of care for patients with PCNSL.

The efficacy of sunvozertinib was superior to that of chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertions. (Funded by Dizal Pharmaceuticals; WU-KONG28 ClinicalTrials.gov number, NCT05668988.).

Accordingly, the antifolate pralatrexate suppressed growth across all seven oncofusions, in multiple human FP-RMS cell lines, and a patient-derived xenograft. These findings demonstrate that divergent FP-RMS oncofusions are functionally fungible through a shared interactome that defines common vulnerabilities.

[This retracts the article DOI: 10.2147/IJN.S150237.].

The system was functionalized with two different anticancer drugs, doxorubicin or pemetrexed, using an on-demand release strategy based on a proteolytic sequence specifically recognized by metalloproteinase-9 (MMP-9), an enzyme overexpressed in various cancers. Based on these results, the platform was later tested on a more disease-specific model, the mesothelioma, to confirm its relevance and adaptability for treating this aggressive cancer. These findings suggest that EPA nanoparticles could serve as a promising drug delivery platform.

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: May 2026 --> Sep 2026

Results from the PAPILLON Chinese mainland population were consistent with the overall population and support the use of amivantamab plus carboplatin-pemetrexed in first-line treatment of Chinese patients with EGFR exon 20 insertion-mutated non-small cell lung cancer.

P1/2, N=13, Active, not recruiting, City of Hope Medical Center | Trial completion date: Feb 2026 --> Feb 2027

The patient initially received pemetrexed plus carboplatin chemotherapy. The treatment efficacy was evaluated as a partial response (PR), with manageable adverse events including skin rash and paronychia. Dacomitinib may provide sustained clinical benefit and an acceptable safety profile in lung adenocarcinoma patients with L747P mutation and bone metastases.

These analyses supported the registration of the weight-tiered Q3W regimen for amivantamab in combination with carboplatin-pemetrexed in the new indications. This work demonstrates how the use of fit-for-purpose pharmacometrics analyses can support dose regimen changes without extensive dose selection clinical studies.