Organ likeDrug Sensitivity Testing Guides Clinical Application of Precise Tumor Treatment

(organoids), con conditional reprogramming (CR) cells, patient derived xenografts (PDX) Functional detection technologies represented by anthropomorphic models such as models bring new options for clinical precision drug therapy [3 ⁃ 5]. Among them, organoids have the advantage of short in vitro operation cycles and high consistency with human derived tissue structures, molecular characteristics, drug reactions, etc., making them widely favored

In the precise treatment of tumors, the most commonly used category of organoids is to guide patients in personalized drug selection based on their drug sensitivity. In order to promote the application of tumor organoid drug sensitivity testing in clinical practice, the Cancer Markers Professional Committee of the China Anti Cancer Association has organized domestic experts in relevant fields to develop this expert consensus based on current domestic and foreign research report data. Due to the fact that the application of organoids in guiding clinical treatment is still in its early stages, this consensus is mainly based on current domestic and foreign reported data, focusing on tumorsDrug sensitivity testing guides clinical application, and this consensus will be revised based on the research progress of tumor like organs in the future.

It has gradually been recommended as one of the in vitro models for clinical guidance of personalized drug use. It has been reported that the accuracy of organ like drugs can reach 80% [12 ⁃ 19], which has attracted extensive attention and active exploration of experts in this field around the world, providing positive evidence for the clinical application of organ like drugs and the formulation of this consensus. Of course, most of the current data are based on observational study and co clinical trial And prospective case reports, but research on tumor organoids is constantly ongoing, especially the results of ongoing or upcoming prospective, interventional, and large-scale clinical studies based on organoids will provide important basis for the revision of this consensus

* Expert consensus: Tumoris an in vitro three-dimensional model directly derived from patient tumor tissue, which has been proven to be highly consistent with the pathological and histological characteristics, molecular characteristics, drug sensitivity, and other aspects of the patient's tumor. At the same time, it has received widespread attention and clinical application exploration from global experts due to its high accuracy in predicting patient efficacy due to drug sensitivity. In clinical practice, physicians can choose based on the specific situation of the patient and with the informed consent of the patient It is recommended to conduct organoid based drug sensitivity testing to provide reference for patients' future medication choices

2 Types of drugs that can be used for tumor organ drug sensitivity testing

& nbsp; With the rapid development of new drug research and development, the number of anti-tumor drugs is increasing. The main types of anti-tumor drugs in clinical practice can be classified into three categories, including cytotoxic drugs (chemotherapy drugs such as paclitaxel, cisplatin/carboplatin, 5-FU, etc.), targeted drugs (drugs targeting EGFR, HER2, VEGFR, etc.), and immunotherapy drugs represented by immune checkpoint inhibitors (PD ⁃ 1 antibodies, PD ⁃ L1 antibodies, etc.). In clinical practice, in order to better kill tumors, most patients receive combination therapy such as chemotherapy drug combination, targeted drug combination chemotherapy, immune drug combination chemotherapy, and targeted combined immunotherapy. Only a small number of patients receive a single chemotherapy drug, targeted drug, or immune drug treatment. TumorDrug sensitivity testing is similar to drug sensitivity testing in vitro cultured cell lines, which can detect both chemotherapy drugs and most targeted drugs; it can detect both single drugs and drug combinations.

For targeted drugs that have been approved for clinical application or are currently undergoing clinical research, the majority of drug applications have clear screening biomarkers for benefit groups. Therefore, gene molecular typing testing is very important for the selection of these drugs, such as EGFR sensitive mutations, ALK/ROS1 fusion, c ⁃ KIT mutations, HER2 overexpression/amplification, KRAS wild-type, MET amplification/mutation, etc. Most targeted drugs specifically target tumor cells for killing, and in addition to drug selection based on gene molecular typing, they can also be used in tumorsDrug sensitivity testing is carried out in order to guide patients to use drugs [18, 20]. In clinical practice, comprehensive judgment will also be made in combination with patients' genetic molecular typing and organoid drug sensitivity testing results [22 ⁃ 23]. However, for some targeted drugs, such as anti angiogenic targeted drugs, before conducting organoid drug sensitivity testing, their specific action sites and mechanisms should also be considered. For example, axitinib (axitinib) works by acting on VEGFR ⁃ 1/2/3 of vascular endothelial cells, but tumor like organs cultured in vitro do not contain vascular structures. Therefore, a separate tumor like organ cannot be used for drug sensitivity testing of anti angiogenic drugs. Drug sensitivity testing can be performed by vascularizing tumor like organs

Immunotherapeutic drugs, such as immunocheckpoint inhibitors, need the participation of tumor immune microenvironment in vivo. Although a relatively low proportion of immune cells can be detected in the first several generations (usually the first 1-2 generations) of tumor like organs cultured from tumor tissue of patients, the number and composition of these immune cells are far from representing the composition of tumor immune microenvironment in patients, so it is not recommended to use separate tumor like organs for drug sensitivity testing of immunotherapeutic drugs, The application of immunotherapy drugs should follow clinical diagnosis and treatment guidelines or consensus. If the future conditions are ripe, it can be passed