PDX Mouse Model - "Private Line" Ancient Tomb Individualized Treatment Plan

Patient-derived tumor xenograft mouse model (PDX model) derived from patient tumor tissue, can be a boon for cancer patients. Individualized PDX models will significantly boost tumor treatment, helping physicians and patients develop a unique and most appropriate treatment plan.

China's cancer deaths have been increasing yearly, ranking first among the causes of death. Data from all over the world show that lung, liver, and colon cancer are still the three most common causes of cancer-related death.

Undoubtedly, the recent new research, the "customized" individualized tumor animal model, that is, the xenograft (PDX) model derived from the patient's tumor tissue, can be a boon for cancer patients, and the individualized PDX model will become a tumor model. It is a great help in treatment, helping doctors to formulate a unique and most suitable treatment plan for patients.

Early detection, diagnosis, and treatment are the critical points of cancer treatment, but the unsatisfactory treatment effect has been plagued by clinical practice.

Of course, the technology to treat tumors has risen in recent years. However, studies have shown that 50% of colon cancer patients relapse and metastasize after treatment, and the resulting high mortality rate is unfortunate! Despite surgical resection and systemic chemotherapy, some patients' conditions deteriorated, and the situation was unsatisfactory. Newer targeted therapies, such as cetuximab and punitive, are widely used to treat metastatic colorectal cancer, but sometimes they don't work at all, depending on the condition of the patient.

Different tumors and different patients; when heterogeneity and polymorphism become obstacles to the treatment of tumors, we begin to call for more individualized treatment plans, which also need to be "customized."

So how can we realize the individualization of tumor treatment?

PDX gives us a good solution. PDX that is, patient-derived xenograft tumor model, is a patient tumor transplanted in immune-deficient mice. They are less differentiated than the original tumor cells, and there are certain differences, but it is the difference between these tumor tissues and the original tumor that can reflect the heterogeneity and adaptability of the tumor after natural selection, so it can provide important, Reliable tumor growth indicators in vivo have created an "in vivo laboratory" that is highly consistent with the patient's physical conditions and can be tested. When the tumor grows larger, the number of mice used for transplantation can be increased, and these mice can be used as a platform to test the drug response, simulating the therapeutic effects of different drugs on the tumor in vivo. Using the PDX model to screen drugs, the results can be used as an assessment of the suitability of treatment, and a more appropriate drug regimen can be obtained, which has stronger specificity for patients and can also improve the success rate of treatment. At the same time, it also reduces the harm caused to the body by the use of multiple drugs by the patient.

In fact, the use of tumor cell line transplantation for individualized tumor therapy has also been studied before. So what is the difference between PDX technology and previous tumor cell line transplantation?

Although these two methods are to implant tumors into experimental mice to study tumor development and so on. However, tumor cell line xenografting is a model established by screening human tumor cells in vitro (in a culture dish), establishing stable cell lines through subculture, and then injecting them into immunodeficient mice subcutaneously, under the kidney capsule or in situ. However, it is clear that the current in vitro culture environment has caused some changes. The tumor microenvironment lacks specific substances such as extracellular matrix and non-tumor cells, which makes the tumor homogeneous after transplantation and cannot express heterogeneity and histopathology. Or the genetic characteristics of the tumor. There are many mutations in the cells of actual tumor patients, which are more conducive to the growth of tumors. The establishment of PDX models is direct transplantation. Although the success rate is relatively low, PDX models can better reflect the genetic diversity of tumors, more realistically simulate the conditions of patients, and better predict the response of tumors to different drugs.

So what can we do with the PDX model?

PDX models have actually been used by multiple institutions to study different tumors. Recently, Korea Surgical Samsung Medical Center and several universities jointly researched and published an article in the journal "Nature." They established PDX models for 241 colon cancer patients, and the success rate was 62.2%. They conducted a 3-year study on these models, revealing the relationship between clinical treatment outcomes and tumorigenesis, and found the relationship between whether patients have KRAS gene mutations and sensitivity to EGFR-targeted drugs. In terms of drug treatment, the study found that when the PDX model is used, there are relatively few patients in the third stage who can be completely cured, and the cure rate can be independently predicted from tumorigenesis (p=0.034), and the mutation of TP53 can often be detected in the third stage patients. The Surgical Clinical Institute of the Gothenburg Academy of Sciences in Sweden published an article reporting that they determined the treatment options for patients with metastatic malignant melanoma through in vitro drug screening and treatment with the MEK inhibitor trametinib on PDX models, and using PDX models, they found that the detection of BRAF Genetic mutations can predict the response to MAPK-targeted therapy. In the journal "Cancer," Justin Stebbing, Keren Paz, and others also reported that in the 16 patients observed, there is indeed a relationship between the clinical treatment outcome and the outcome of tumor transplantation. They believe that the PDX model can guide the treatment of rare tumors, such as sarcoma.

Conclusion: The PDX model can be used to predict the therapeutic effect of drugs on tumors. It provides important guidance and a basis for formulating clinical individualized treatment plans and will also promote the smooth progress of more studies on tumor drugs and gene mutations. Realize the individualized treatment of tumors, and sincerely hope that such "private customization" can improve the quality of life of patients!

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