Cancer cell lines are essential research tools in drug discovery. They are widely used and contribute to the development of many drugs, especially in preclinical anticancer pharmacology research. Cancer cells are very easy to handle because they have acquired the ability to proliferate infinitely and grow logarithmically in culture dishes. In the early days of the use of cancer cell lines, many cancer cell lines based on different tissues and organs of origin were established and registered in cell banks and made available. On the other hand, cancer cell lines, which are mainly used in two-dimensional culture, have problems such as the fact that they cannot be distinguished from cancer cells in living organisms because only cells that proliferate rapidly in culture dishes are selected. However, the technology is expected to be further utilized since it is very useful for detailed analysis of cancer cells and for genetic modification such as genome editing.

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This study established a panel of patient-derived spheroids from ovarian cancer clinical materials to explore the chemoresistance mechanisms. A systematic evaluation using platinum-based compounds showed variable sensitivities among the spheroids. Integrative analyses combining gene expression profiling and chemoresistance data highlighted the role of glucose-6-phosphate dehydrogenase （G6PD） and glutathione-producing enzymes in conferring cisplatin resistance. Elevated G6PD levels correlated with poor prognosis and enhanced resistance, whereas treatment combining a G6PD inhibitor with cisplatin significantly reduced spheroid proliferation and peritoneal metastasis in mouse models. These findings emphasize the importance of patient-derived cells and integrated approaches in uncovering molecular bases of drug resistance in cancer.

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With the development of organoid culture methods, it is now possible to culture organoids for a variety of cancer types. Cancer organoids are culture models that retain the characteristics of patient cancer, especially plasticity and diversity. Because organoid culture can now be performed from a patient’s tumor in a short time and has shown a high success rate in some cancer types, it is expected to be used not only in personalized medicine to select the best treatment for each patient, but also in drug discovery, including screening and biomarker development. As a means of assessing the response of cancer cells, it is expected to be used as a complement to the snapshot-like information such as genomics information. This paper describes the current application of cancer organoid culture to pharmaceutical research and presents issues that need to be resolved.

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Tumors continue to claim the lives of a large number of people worldwide. Oncology research, anticancer drug discovery, and the development of personalized medicine are being actively pursued. However, existing tumor model systems, such as static 2D and 3D culture systems and animal models, are not completely representative of actual tumors. “Tumors-on-chip” that simulate tumors in vitro using fluidic devices could solve this gap and enable the achievement of results not possible with existing tumor model systems. In this review, we identify five design patterns common to the numerous tumor chips and clarify the characteristics of each, taking into account the latest research trends. This review could serve as a valuable guide when using or designing tumors-on-chip.

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A cell line-derived xenograft（CDX）model, prepared by transplanting human cancer cell line into mice, has been used in pharmacological cancer research for more than half a century. Even now, CDX models are adopted to evaluate pharmacological characteristics of various therapeutic modalities, including low-molecular-weight compounds, peptide, nucleic acid, antibody therapeutics, and cell-based therapy. However, in recent years, there are many reports indicating that tumor microenvironments in CDX tumors do not reflect that in clinical tumors. Therefore, it has been considered that CDX models are not an optimal cancer model for drug screening in preclinical study. Nevertheless, we believe that CDX model is still an important and useful model for pharmacological research, especially for an education of DDS efficacy due to its case of model generation, high reproducibility and high throughput. In this review, we’d like to introduce the immunodeficient mice and transplantation for preparation of CDX models, and pharmacological cancer research using them. Moreover, we describe our previous works as an example of pharmacological cancer research using CDX models.

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A patient-derived xenograft （PDX） model was established by directly transplanting surgically resected human tumor tissue into immunodeficient mice without in vitro culture, followed by maintenance through in vivo passage. This model helped retain the histological structure, cell morphology, and molecular and genetic properties of human tumor tissues. As a model that reflects the diversity and complexity of tumors, it can be used in the research and development of molecularly targeted drugs. Although PDX models are valuable research tools, the development and utilization of established PDX lines require different research plans compared to those commonly used for in vitro cultured tumor cell lines. This section describes the characteristics of PDX models as tumor models and elucidates the points to consider when attempting to establish and use PDX models.

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Delgocitinib is a novel Janus kinase（JAK） inhibitor discovered by Japan Tobacco Inc. based on its inhibitory activity against human JAK1, JAK2, JAK3, and tyrosine kinase 2. CORECTIM^Ⓡ Ointment 0.5％ containing Delgocitinib was launched as a topical JAK inhibitor for the first time in the world in June 2020, and 0.25％ Ointment was launched in the following year. In the formulation of CORECTIM^Ⓡ Ointment, the physicochemical stability of drug substance, the physical property evaluation of the ointment, sensuality and stability evaluation were performed, and it was necessary to develop a formulation with excellent usability and stability. The development history, formulation development, pharmacokinetics, and clinical study results of CORECTIM^Ⓡ Ointment are also described here.

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