As the incidence and mortality of cancer have increased year by year, cancer has become the primary enemy threatening human health. Therefore, more and more researchers have invested in the exploration of cancer pathogenesis and new treatments. Despite this, only a handful of new anti-cancer drugs are approved every year. The main reason is that most new drugs with good preclinical effects lack good clinical efficacy. Therefore, rational application and evaluation of innovative preclinical anti-cancer drugs System to promote the combination and unification of preclinical research and clinical efficacy is particularly urgent and important.
This article summarizes the five most common mouse cancer models and their advantages and disadvantages for everyone to weigh and choose when designing a drug efficacy evaluation program.
Medicilon has established a complete evaluation system for preclinical anti-tumor efficacy, and has more than 200 different types of tumor efficacy models, including xenogeneic tumor transplantation models, orthotopic tumor transplantation models, homologous tumor transplantation models, and transgenics Mouse tumor models, humanized tumor transplantation models, and the use of radiotherapy and chemotherapy combined treatment evaluation technology, can treat cytotoxicity and target small molecule drugs, monoclonal antibodies and bispecific antibodies and other macromolecular drugs, ADC, CAR-T cells Provide comprehensive and systematic evaluation of new anti-tumor drugs.
Cell-derived xenograft (CDX) model
The traditional tumor model is to screen human tumor cells in vitro, establish a stable cell line through subculture, and then inject them into immunodeficient mice. This model is called cell line-drived xenotransplantation. xenografts, CDX) model.
• Short modeling time, good repeatability and low cost;
• Closer to the biological characteristics of tumor cells in the human body;
• Small individual differences;
• The method is mature.
• Cannot simulate the problems of clinical treatment, such as host immune response, tumor heterogeneity and tumor microenvironment.
List of Medicilon xenograft models
Genetically engineered mouse (GEM) model
The construction of GEM model is to use genetic engineering technology to edit the genome of embryonic stem cells or fertilized eggs, and edit specific tumor suppressor genes or oncogenes in specific types of cells in mice to generate specific tumors , including traditional transgenes Mouse, TetraOneTM genetically engineered mouse, transcription activator-like effector nuclease (TALEN) genetically engineered mouse model and model mouse developed by CRISPR-Cas9 genome editing technology.
• This model is the most comprehensive and complete simulation of cancer, which is helpful for the study of cancer evolution mechanism and dynamics, key mutant genes, tumor microenvironment and metastasis and invasion mechanisms;
• Provide objective and accurate preclinical evaluation results.
• Genetic differences between species will affect the accuracy of the method;
• Multiple mutations of genes will affect the evaluation of drug efficacy;
• Limitations of the screening scale, high cost and long time for modeling.
List of Medicilon orthotopic transplantation models, allogeneic tumor transplantation models, humanized tumor transplantation models, and transgenic mouse tumor models
GEM-derived allograft (GDA) model
The GDA model is constructed by labeling specific GEM-derived tumor tissue fragments with fluorescent markers, and then subcutaneously transplanting them into a homologous host for growth.
• Especially suitable for in situ and metastatic tumors, it is convenient to observe the development process of in situ tumors, and simulate the process of tumor recurrence and metastasis after clinical surgery to remove the in situ tumor;
• The simulation is very similar;
• It avoids the situation that GEM has a long time for tumor formation and uneven growth.
• Animal cancer models established through transplantation may deviate from the characteristics of Qin Dynasty samples.
Human-derived tumor xenografts (PDTX)
The model established by transplanting the patient’s fresh tumor tissue into immunodeficient mice is called PDTX (patient-derived tumor xenografts) model.
• Compared with human tumors and primary tumors, it has maintained molecular, genetic and pathological characteristics;
• Suitable to solve the problems encountered in the treatment of individual cancer.
Humanized tumor model (Hu-PDX)
Human hematopoieticstem cells (HSCs) were transplanted into X-ray irradiated mice with severe immunodeficiency, and then the patient’s tumor tissue was transplanted into the mice to establish a humanized patient-derived xenograft (Hu- PDX).
• Provide a growth environment more similar to the human body;
• Contains human immune cells, cytokines and other components.
• Hematopoietic stem cells are not easy to obtain in large quantities;
• The rebuilding process of the mouse immune system is long and expensive.
Modern oncology research uses a variety of model systems, which can improve the success rate of clinical treatment by establishing a pre-clinical evaluation platform, which has a good application prospect. Each model system has its own unique value, and all systems play an important role in future preclinical research. Different preclinical cancer models suggest the need to continuously expand knowledge to promote the development of effective preclinical platforms. In the future, we can use genetic engineering technology to develop effective treatment methods, and the combined use of multiple model systems will also become the only way for the development of preclinical cancer models.
The Pharmacology Department of Medicilon provides tips for the clinical research of customers’ new drug research and development projects through a complete tumor efficacy evaluation system, avoids unnecessary waste, reduces the workload of clinical research, and promotes the process of new drug development!
Medicilon (stock code: 688202) is a drug development outsourcing service company (CRO). Founded on February 2, 2004, the company has gone through 16 years and established a company in Shanghai that integrates compound synthesis, compound activity screening, structural biology, pharmacodynamic evaluation, pharmacokinetic evaluation, toxicological evaluation, and formulation research A comprehensive technical service platform that conforms to international standards and is integrated with new drug registration, and has been recognized by the international drug management department. Medicipua’s animal laboratory facilities have obtained AAALAC (International Association for Animal Evaluation and Certification) certification and National Medical Products Administration NMPA GLP certification, and have reached the US Food and Drug Administration GLP standard.
Medicilon has a wealth of experience in global cooperation. Since 2015, Medicilon has served more than 500 active customers worldwide. It has served many global pharmaceutical companies such as Takeda Pharmaceuticals, Johnson & Johnson Pharmaceuticals, GlaxoSmithKline, Roche Pharmaceuticals, etc. R&D outsourcing services are provided by well-known domestic and foreign customers such as Swiss Medicine, Yangzijiang Pharmaceutical, CSPC, Huahai Pharmaceutical, and Zhongsheng Pharmaceutical.
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