In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefo...In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.展开更多
Cancer drug development is a time and resources consuming process.Around 90%of drugs entering clinical trials fail due to lack of efficacy and/or safety issues,more often after conspicuous research and economic effort...Cancer drug development is a time and resources consuming process.Around 90%of drugs entering clinical trials fail due to lack of efficacy and/or safety issues,more often after conspicuous research and economic efforts.Part of the discarded drugs might be beneficial only in a subgroup of the study patients,and some adverse events might be prevented by identifying those patients more vulnerable to toxicities.The implementation of pharmacogenomic biomarkers allows the categorization of patients,to predict efficacy and toxicity and to optimize the drug development process.Around seventy FDA approved drugs currently present one or more genetic biomarker to keep in consideration,and with the progress of Precision Medicine tailoring therapies on individuals’genomic landscape promises to become a new standard of cancer care.In the current article we review the role of pharmacogenomics in cancer drug development,underlying the advantages and challenges of their implementation.展开更多
文摘In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.
文摘Cancer drug development is a time and resources consuming process.Around 90%of drugs entering clinical trials fail due to lack of efficacy and/or safety issues,more often after conspicuous research and economic efforts.Part of the discarded drugs might be beneficial only in a subgroup of the study patients,and some adverse events might be prevented by identifying those patients more vulnerable to toxicities.The implementation of pharmacogenomic biomarkers allows the categorization of patients,to predict efficacy and toxicity and to optimize the drug development process.Around seventy FDA approved drugs currently present one or more genetic biomarker to keep in consideration,and with the progress of Precision Medicine tailoring therapies on individuals’genomic landscape promises to become a new standard of cancer care.In the current article we review the role of pharmacogenomics in cancer drug development,underlying the advantages and challenges of their implementation.
