Lenvima (lenvatinib)

We describe a patient with radioactive iodine-refractory, metastatic oncocytic thyroid carcinoma with an NBN gene (c.2166_2167delGCinsAT) pathogenic variant, who developed progressive disease despite receiving systemic therapy with lenvatinib and pembrolizumab. A mutual exclusivity analysis demonstrated a tendency for pathogenic variants in one MRN complex genes to co-occur with pathogenic variants in the other two MRN complex genes. In conclusion, the MRN complex pathogenic variants could be potentially oncogenic in TCs and may be linked to aggressive forms of TC.

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and the available targeted therapies (e.g., sorafenib, lenvatinib) have limited options and frequent drug resistance. These compounds synergize with conventional targeted agents to overcome drug resistance through direct cytotoxicity or targeting hypertrophic lysosomal drug release. This article reviews the regulation of LDCD and the role of natural products in HCC based on PubMed, Web of Science and CNKI databases, aiming to providing a reference for the treatment of drug-resistant liver cancer.

Combination treatment with GLP-1RA and Lenvatinib significantly inhibited tumor cell growth in resistant models. These findings suggest that the AMPKα1/HIF-1α/PFKFB3 axis represents a metabolic vulnerability in Lenvatinib-resistant HCC and support GLP-1RA-based combination strategies.

In vivo, it exerted more potent tumor growth inhibition without obvious toxicity, further downregulated PD-L1/VEGF, enhanced intra-tumoral T cell and M1 macrophage infiltration, and increased systemic T lymphocyte proportions. Fluvoxamine combined with lenvatinib exerts synergistic anti-HCC activity and is associated with enhanced antitumor immune infiltration, providing experimental evidence for novel clinical HCC combination therapies.

ABHD17C promotes an immunosuppressive tumor microenvironment and attenuates the anti-tumor effects of lenvatinib in HCC. Targeting ABHD17C may represent a potential strategy to enhance lenvatinib sensitivity and improve therapeutic outcomes.

P2, N=70, Recruiting, Peking Union Medical College Hospital

Advanced RAI-R TC candidates for systemic therapy often harbor gene alterations. An adequate result was less frequently achieved in cases of RNA-based NGS than in DNA-based NGS, especially if the interval between tissue collection and molecular analysis was longer; nevertheless, the limited cohort size precludes definitive conclusions.

Notably, combined treatment with the MAPK inhibitor selumetinib and lenvatinib synergistically overcomes drug resistance in lenvatinib-resistant xenograft models. Collectively, our findings identify USP32 as an important regulator of HCC malignancy and lenvatinib resistance via the DDX17/miR-3163/MAPK axis, highlighting its potential as a therapeutic target in refractory HCC.

P2, N=29, Completed, Massachusetts Eye and Ear Infirmary | Active, not recruiting --> Completed

Current research hotspots regarding immune checkpoint inhibitors in the treatment of endometrial cancer include microsatellite instability, mismatch repair deficiency, PD-1, PD-L1, chemotherapy, pembrolizumab, lenvatinib, and dostarlimab. This study systematically analyzes the current state of research in this field, focusing on research hotspots, emerging trends, and future development directions. Additionally, it comprehensively evaluates the most influential literature, core journals, authoritative scholars, leading research institutions, and major contributing countries in this field.

In vivo studies using Huh7 xenograft models showed that TP-LEN combination significantly suppressed tumor growth without causing hepatic or renal dysfunction, accompanied by marked downregulation of CERK, GPX4, and SLC7A11 in tumor tissues. This study confirms that TP enhances LEN sensitivity by targeting the CERK/sphingolipid-ferroptosis axis, providing a novel strategy to overcome HCC resistance.

Erythrocytosis represents an underrecognized, early, recurrent, and indolent adverse event of antiangiogenic and targeted therapies, particularly RETi, in advanced thyroid cancer. Its biological mechanisms and optimal management strategies warrant further investigation.