Optimizing anticancer therapeutics needs to account for variable drug responses in heterogeneous cell populations within the tumor as well as in organs of toxicity. To address cell heterogeneity, we propose a multiscale modeling approach—from in vitro to preclinical and clinical studies—to develop cell-type–specific pharmacokinetic–pharmacodynamic (PK-PD) models. A physiologically based mechanistic modeling approach integrating data from aqueous solutions, U87 glioma cells, mice, and cancer patients was utilized to characterize the brain disposition of temozolomide (TMZ), the cornerstone of chemotherapy against glioblastoma multiforme. The final model represented intracellular normal brain and brain tumor compartments in which TMZ pH-dependent conversion to the DNA-alkylating species leads to the formation of DNA adducts that serve as an entry point for a PD model. This multiscale protocol can be extended to account for TMZ PK-PD in different cell populations, thus providing a critical tool to personalize TMZ-based chemotherapy on a cell-type–specific basis.

Mucinous cystic neoplasm of the liver (MCN) is uncommon and sometimes misdiagnosed as Echinococcal cyst, especially when patient with history of echinococcus infection. We report an asymptomatic 60 year-old woman with history of echinococcal cyst in the liver which was resected approximately 20 years ago, developed a new liver cystic lesion approximately 7 years after resection. Contrast enhanced computed tomography demonstrated a 7.4 x 5.6 x 5.4 cm cystic lesion in the right hepatic lobe with thin septations and no enhancing solid components. Though the serum antibody to Echinococcus was negative, the diagnosis of Echinococcal cyst was made and the patient was started empirically on Echinococcal therapy based on her clinical history and imaging findings. Post treatment CT scan showed that the cyst continued to grow. A partial right lobectomy was performed and the final diagnosis was mucinous cystic neoplasm of the liver (MCN).

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