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Selective internal radiation with Y-90 resin microspheres (SIRT) for liver metastases of gastro-intestinal stromal tumors (GIST) resistant to tyrosine kinase inhibitor (TKI) therapy

Hepatic metastases of GIST might be the dominant site of progression and resistant to available tyrosine kinase inhibitors (TKIs). Selective internal radiation therapy (SIRT) offers treatment by intratumoral radiation up to 200 Gy. We analyzed the hepatic progression-free survival (H-PFS) in a consecutive patient cohort.

Increased potentiation of 5-fluorouracil induced thymidylate synthase inhibition by 5,10-methylenetetrahydrofolate (arfolitixorin) compared to leucovorin in patients with colorectal liver metastases; The Modelle-001 Trial

5-Fluorouracil (5-FU) is a cornerstone in treatment of colorectal cancer (CRC) and is usually combined with leucovorin (LV) to enhance the antitumour effect by increase thymidylate synthase (TS) inhibition, the key target enzyme for 5-FU. Arfolitixorin (Arfo) is an active form of the reduced folate, [6 R]-5,10-methylenetetrahydrofolate ([6 R]-MeTHF and in contrast to LV, does not need to be metabolized. The Modelle-001 was designed to explore whether a single intravenous bolus injection of Arfo as compared to LV, together with 5-FU increases the inhibition of TS, levels of folate concentrations and polyglutamylation in CRC liver metastases (CRLM) and liver parenchyma.

A detoxified TLR4 agonist inhibits tumour growth and lung metastasis of osteosarcoma by promoting CD8+ cytotoxic lymphocyte infiltration

Osteosarcoma is the most common malignant bone tumour with limited treatment options and poor outcomes in advanced metastatic cases. Current immunotherapies show limited efficacy, highlighting the need for novel therapeutic approaches. Systemic immune activation by Toll-like receptor 4 (TLR4) immunostimulants has shown great promise; however, current TLR4 agonists’ toxicity hinders this systemic approach in patients with osteosarcoma.

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