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In addition to their cytotoxic effects, many small-molecule agents exhibit insufficient penetration into critical sanctuary sites, including granulomas, the blood-brain barrier (BBB), and various intracellular compartments, where pathogens can persist and facilitate relapse (Pardridge, 2020

Patients who are homozygous or compound heterozygous for no function DPYD variants (i.e., carry two no function DPYD variants) or are compound heterozygous for a no function DPYD variant plus a decreased function DPYD variant have complete DPD deficiency and are at increased risk for acute early-onset of toxicity and serious life-threatening, or fatal adverse reactions due to increased systemic exposure to XELODA

Costello JL, Castro IG, Hacker C, Schrader TA, Metz J, Zeuschner D, Azadi AS, Godinho LF, Costina V, Findeisen P, Manner A, Islinger M, Schrader M (2017) ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER

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