Drug Delivery, Uptake & IPTLD Mechanism
Clinical Application and Drug Resistance Mechanism of Gemcitabine
Zhang X, Qi B, Chen J.
Open-access review explaining why many chemotherapy drugs cannot simply diffuse into a cancer cell. It confirms that this class of chemotherapy is water-soluble and "must rely on nucleoside transporters on the cell membrane" to get inside, that reduced transporter function lowers drug uptake and causes resistance, and that the enzyme deoxycytidine kinase performs "the rate limiting step of drug activation" once the drug is inside. It also notes that greater accumulation of the activated drug within tumour cells correlates with prolonged survival. This is the published basis for the two-gate model described on our IPTLD science page.
Mebendazole and Temozolomide in Patients With Newly Diagnosed High-Grade Gliomas: Results of a Phase 1 Clinical Trial
Gallia GL, Holdhoff M, Brem H, et al.
Johns Hopkins phase 1 dose-escalation trial in 24 patients with newly diagnosed high-grade glioma. Establishes safety of mebendazole up to 200 mg/kg/day alongside standard temozolomide, with reversible grade 3 liver enzyme elevation at the highest dose. Reported median overall survival of 21 months, but the authors caution the study was single-arm, included both WHO grade III and IV tumours, and is subject to sample bias - so efficacy remains undetermined. A clear example of why monitored, supervised use detects toxicity that self-medication would miss.
A Phase I/II Study Evaluating the Safety and Efficacy of Ivermectin in Combination With Immune Checkpoint Inhibitor in Patients With Metastatic Triple Negative Breast Cancer
Yuan Y, Mita M, Shiao S, et al. (Cedars-Sinai Medical Center)
The official trial registry record - the primary source, rather than a summary of it. Patients can read the full protocol, eligibility criteria, dosing schedule and current status directly. Estimated enrolment 34, opened October 2023, still recruiting, with no results yet posted. Useful for anyone wanting to see exactly what is and is not yet known about ivermectin in cancer.