Lenvima (lenvatinib)

For cases lacking these specific markers, VEGFR-targeted multikinase inhibitors (e.g., lenvatinib) remains the standard of care for RAIR-DTC...The therapeutic paradigm in thyroid cancer is shifting from non-selective multikinase inhibition toward molecularly matched, combination-based, and adaptively sequenced strategies. Early and comprehensive genomic profiling-including fusion detection-is essential to optimize treatment selection, address resistance, and expand precision therapy options across disease subtypes.

Importantly, targeting NDST2 via genetic ablation or inhibition using a CaCO₃-nanoparticle-based siRNA delivery system effectively reversed lenvatinib resistance in HCC tumor models. These findings establish NDST2-driven EGFR N-glycosylation as a critical mechanism of lenvatinib resistance in HCC and highlight NDST2 as a promising therapeutic target for restoring drug sensitivity.

Although paclitaxel and lenvatinib have been used as drug treatments, combination therapy with dabrafenib and trametinib has recently been reported to be effective. Furthermore, lenvatinib, a molecularly targeted agent, shows limited efficacy against ATC and is associated with frequent adverse events. In contrast, combination therapy with dabrafenib and trametinib is considered an effective therapeutic option for patients with BRAF V600E mutation-positive ATC, when appropriate management and monitoring are implemented.

Leveraging these insights, canagliflozin, an FDA-approved SGLT2 inhibitor, was repurposed as a direct HSPA6-targeting compound that disrupted this resistance axis, restored ferroptosis sensitivity, and synergized with lenvatinib in patient-derived models. This work unveils a dynamic, condensate-driven mechanism of drug resistance and offers a readily translatable strategy to overcome lenvatinib resistance in HCC.

A 62-year-old man with metastatic PSA underwent splenectomy followed by first-line paclitaxel, achieving stable disease for 7 months...Sequential treatment with liposomal doxorubicin, eribulin, toripalimab, and lenvatinib failed to control the disease failed to control the disease...To our knowledge, this is the first reported use of inavolisib in angiosarcoma. The rapid biochemical and radiological response observed in this PIK3CA-mutated PSA supports early genomic profiling to identify actionable alterations and warrants prospective evaluation of combined phosphoinositide 3-kinase and vascular endothelial growth factor pathway inhibition in refractory angiosarcoma.

This research pioneers the identification of anlotinib as an ER stress- and autophagy-dependent ICD inducer in HCC. Our comprehensive mechanistic dissection and robust preclinical evidence establish anlotinib's ability to convert immunologically "cold" tumors to "hot" ones through the FGFR-1/ER stress/autophagy/DAMP release axis. The synergy with anti-PD-1 and enhancement by metformin provide a rationale for novel combination strategies to overcome current limitations of targeted-immunotherapy, offering a promising approach to improve response rates in advanced HCC.

Peroxisomes act as pivotal regulators of digestive cancer progression by modulating signaling pathways, the TIME, therapeutic resistance, and lipid metabolism. Targeting peroxisomal function, particularly in high-risk subgroups of HCC and CRC, warrants further exploration as a promising therapeutic strategy.

These findings suggest that lenvatinib suppresses osteosarcoma cell proliferation, migration, and invasion, at least in part, by inducing ferroptosis-related changes associated with modulation of the p-STAT3/p53/xCT axis. This study reveals a previously underrecognized mechanism of lenvatinib action and supports further investigation of ferroptosis-targeted strategies in osteosarcoma.

P2, N=30, Active, not recruiting, Tianjin Medical University Cancer Institute and Hospital

P1/2, N=56, Not yet recruiting, IRCCS Istituto Nazionale Tumori Fondazione Pascale

Immunotherapy is a cornerstone in advanced EC management, guided by molecular classification. Key challenges include limited efficacy in pMMR tumors, lack of robust predictive biomarkers, and uncertainty in treatment sequencing. Future strategies should focus on biomarker-driven approaches and rational combinations.

Genetic testing confirmed sensitivity to dostarlimab-gxly and pembrolizumab, leading to the initiation of pembrolizumab (200 mg Q3W) and lenvatinib (20 mg QD) in June 2024 after spine surgery. We present a 57-year-old female patient initially diagnosed with FIGO Stage 2 EC, who subsequently developed distant metastases and was restaged as FIGO Stage 4B recurrent disease. The management of this patient illustrates the multimodal treatment approach and the critical role of molecular subtyping in guiding immunotherapeutic strategies for recurrent advanced EC.