Abstract
Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Molecular targeted therapies with remarkable efficacy are currently in use against various tumors. Thus, there is a need for in vitro functional-potency assays that can be used to test the efficacy of molecular targeted drugs and model complex interactions between immune cells and tumor cells to evaluate the potential for cancer immunotherapy. This study represents an in vitro evaluation of different classes of molecular targeted drugs, including small-molecule inhibitors, monoclonal antibodies, and an antibody-drug conjugate, using lung PDOs. We evaluated epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) inhibitors using a suitable high-throughput assay system. Next, the antibody-dependent cellular cytotoxicity (ADCC) activity of an anti-HER2 monoclonal antibody was evaluated to visualize the interactions of immune cells with PDOs during ADCC responses. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using PDOs. Our results demonstrate that the in vitro assay systems using PDOs were suitable for evaluating molecular targeted drugs under conditions that better reflect pathological conditions.
Highlights
Molecular targeted therapy is one of the most important paradigm shifts in the history of cancer therapy
We suggest that assay systems based on F-Patient-derived tumor organoids (PDOs) may be utilized to evaluate anticancer agents under conditions that better reflect clinical conditions and to discover markers of the pharmacological effects of anticancer agents
100 μg/mL trastuzumab at 120 h, but RLUN21 clusters treated with 10 μg/mL trastuzumab did not show differences after 3 h. These results imply that the invasion of THP-1 cells into the cell clusters causes the cytolysis of RLUN21. These results revealed that these F-PDOs can be used for evaluating the efficacies of neutralizing activity, antibody-dependent cellular cytotoxicity (ADCC) activity, and antibody-drug conjugates (ADCs)
Summary
Molecular targeted therapy is one of the most important paradigm shifts in the history of cancer therapy. Traditional anticancer chemotherapeutic agents block cell division and DNA replication, and reduce the size of tumors. Cells 2019, 8, 481 survival, they are not effective for all types of cancer and induce side effects. Molecular targeted drugs have been developed that interfere with specific molecules to block cancer growth, progression, and metastasis [1,2,3]. Many molecular targeted drugs have demonstrated remarkable clinical success in treating myriad types of cancer, including breast, leukemia, colorectal, lung, and ovarian cancer. Targeting the immune system, which accelerates anti-tumor activity through immune checkpoint inhibition, is proving to be an increasingly effective method for treating various cancers, prolonging life, and increasing progression-free survival [1,2,3]. Molecular targeted approaches continue to be limited by wide variations in the degree and durability of patient responses and side effects, and numerous cancers remain completely refractory to such therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
