跳至主要内容

What is a PDX mouse model and what are PDX models used for?

In this article, I will introduce you to the PDX model, its history and development, advantages over traditional cancer models, applications in cancer treatment and drug development, success stories, challenges and limitations, future prospects, collaboration and partnerships, and my conclusion.

Introduction to the PDX model

The PDX model, also known as patient-derived xenograft, is a preclinical cancer model that involves transplanting cancer cells directly from a patient's tumor into an immunodeficient mouse. The mouse is then used to study the tumor's biology, response to treatment, and drug efficacy. The PDX model is considered a more accurate representation of human cancer than traditional cancer models, such as cell lines and mouse models, because it retains the heterogeneity and complexity of the patient's tumor. Now, Medicilon have the PDX models covering colon cancer, lung cancer, gastric cancer, breast cancer, liver cancer, pancreas cancer.



History and development of the PDX model

The first PDX model was developed in the early 1990s by transplanting human leukemia cells into immunodeficient mice. Since then, the PDX model has been adapted to various types of cancer, including breast, lung, prostate, and colon cancer. The PDX model has also been used to study cancer metastasis and drug resistance. The development of the PDX model was driven by the need for better preclinical models that accurately predict clinical outcomes.

Advantages of the PDX model over traditional cancer models

The PDX model has several advantages over traditional cancer models. Firstly, it retains the heterogeneity and complexity of the patient's tumor, which is crucial for studying cancer biology and drug response. Secondly, it allows for the testing of multiple drugs simultaneously, which can accelerate drug development and reduce costs. Thirdly, it can predict clinical outcomes more accurately than traditional cancer models, which can reduce the failure rate of clinical trials. Lastly, it can be used to study rare and aggressive cancers that are difficult to model in vitro.

How the PDX model works

The PDX model involves several steps. Firstly, a patient's tumor is obtained through biopsy or surgery. Secondly, the tumor is fragmented and transplanted into an immunodeficient mouse. Thirdly, the tumor is allowed to grow in the mouse until it reaches a certain size. Fourthly, the mouse is treated with different drugs, either alone or in combination, to test their efficacy. Lastly, the tumor is harvested and analyzed to study its biology and drug response.

Applications of the PDX model in cancer treatment and drug development

The PDX model has several applications in cancer treatment and drug development. Firstly, it can be used to identify new drug targets and test the efficacy of novel drugs. Secondly, it can be used to study drug resistance and develop strategies to overcome it. Thirdly, it can be used to personalize cancer treatment by selecting the most effective drugs for individual patients. Fourthly, it can be used to study the biology of cancer metastasis and develop therapies to prevent it.

Success stories of the PDX model in cancer research

The PDX model has already shown promising results in cancer research. For example, a PDX model of triple-negative breast cancer (TNBC) was used to identify a new drug target, CDK7, that was found to be overexpressed in TNBC patients. The PDX model was also used to test the efficacy of a new drug, THZ1, that targets CDK7, and found to be effective in reducing tumor growth. Another success story is the use of PDX models to study drug resistance in non-small cell lung cancer (NSCLC) and develop combination therapies that overcome resistance.

Challenges and limitations of the PDX model

The PDX model also has several challenges and limitations. Firstly, it is time-consuming and expensive to develop and maintain PDX models. Secondly, the engraftment rate of patient tumors into mice can vary and depend on several factors, such as the mouse strain and the tumor type. Thirdly, the PDX model may not fully represent the complexity of the patient's tumor microenvironment, which can affect drug response. Lastly, the ethical implications of using animals in cancer research need to be considered.

Future of the PDX model in cancer research

Despite the challenges and limitations, the PDX model has a bright future in cancer research. Advances in technology, such as CRISPR/Cas9 gene editing and organoid culture, can enhance the accuracy and efficiency of PDX models. Collaboration and partnerships between academia, industry, and patient advocacy groups can also accelerate the development and application of PDX models. The PDX model can also be used to study the effects of immunotherapy and combination therapies, which are promising approaches in cancer treatment.

Collaboration and partnerships in the PDX model

Collaboration and partnerships are crucial for the success of the PDX model. Academia can provide expertise in cancer biology and drug development, while industry can provide resources and funding for clinical trials. Patient advocacy groups can provide valuable input on patient needs and preferences. The PDX model can also benefit from international collaboration and standardization of protocols and data sharing. The ultimate goal of collaboration and partnerships is to translate PDX model research into clinical applications that benefit patients.

Conclusion

In conclusion, the PDX model is an innovative preclinical cancer model that has the potential to revolutionize cancer treatment and drug development. The PDX model retains the heterogeneity and complexity of the patient's tumor, allows for the testing of multiple drugs simultaneously, predicts clinical outcomes more accurately, and can be used to study rare and aggressive cancers. The PDX model has already shown promising results in identifying new drug targets, overcoming drug resistance, and personalizing cancer treatment. However, the PDX model also has challenges and limitations that need to be addressed. Collaboration and partnerships are crucial for the success of the PDX model in translating research into clinical applications that benefit patients.

Medicilon's PDX Model

Now, Medicilon have the PDX models covering colon cancer, lung cancer, gastric cancer, breast cancer, liver cancer, pancreas cancer. Our research on PDX model includes molecular level genotyping and pharmacological efficacy evaluation service of orthotopic model, promising great prediction for clinical efficacy research.

 

评论

此博客中的热门博文

What is preclinical testing?

In the process of  preclinical testing  of a compound or biological agent into a drug, the compound involved must go through the testing phase. First, we need to identify potential targets that can treat the disease. Then, a variety of compounds or preparations are screened out. Any compound that has shown potential as a drug for the treatment of this disease needs to be tested for toxicity before clinical testing to reduce the possibility of injury. preclinical testing What is the basis of preclinical testing? According to US Food and Drug Administration (FDA) regulations, a series of tests are required before a new drug is approved for use. In the first stage, basic research determines a hypothetical target for the treatment of a certain disease, and then screens small molecules or biological compounds to discover any substance with the potential to treat the disease. Then, a  preclinical research  phase followed, before which, as described above, the potential toxicity of the compou

Inventory of the three major in vitro pharmacokinetic research methods

  The metabolic properties of a compound are an essential factor in whether or not it can be used as a drug in the clinical setting, so pharmacokinetic studies of newly synthesized compounds are required in drug development. In vitro incubation with liver microsomes, recombinant CYP450 enzyme lines, and in vitro incubation with hepatocytes are some of the more common in vitro drug metabolism methods. 1. In vitro incubation method with liver microsomes The metabolic stability and metabolic phenotypes of candidate compounds in different species of liver microsomes are good predictors of the metabolic properties of compounds in vivo. They are practical tools for evaluating candidate compounds in the pre-development phase of drug development. Liver microsomes include rat liver microsomes, human liver microsomes, canine liver microsomes, monkey liver microsomes, and mouse liver microsomes. In in vitro incubation of the liver, microsomes are the "gold standard" for in vitro d

Novel Parkinson’s Therapies Possible with New Mouse Model

Parkinson's disease (PD) is a neurodegenerative disorder that is marked by the accumulation of the protein, α-synuclein (αS), into clumps known as Lewy bodies, which diminish neural health. Now, researchers from Brigham and Women's Hospital (BWH) report the development of a mouse model to induce PD-like αS aggregation, leading to resting tremor and abnormal movement control. The mouse responds to L-DOPA, similarly to patients with PD. The team's study (“Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson’s Disease”) on the use of this transgenic mouse model appears in  Neuron . “α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in PD. Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutati