Mouse avatars, or avatar mice, refers to an experimental method employed to identify the best chemotherapeutic choice for a particular cancer patient.
The method was originally employed to treat cancer patients by Dr. Manuel Hidalgo (Spanish National Cancer Research Center in Madrid). [1] The name mouse avatar or avatar mice was originally coined by the Spanish National Cancer Research Center [2] and was subsequently popularized by the journals Nature [3] and Science , [4] the Mayo Clinic [5] and The New York Times [6] among others. [7] [8]
Generally, mouse avatars involve three steps, as follows: [9]
The tumor is obtained by surgical resection. This may cure the patient. The tumor however may regrow, at the same or at a distant location (metastasis), a process that usually entails several months. If this happens, the avatar mice may guide the oncologist to choose the most efficient chemotherapeutic treatment.
Fresh pieces of the tumor are implanted into mice (these are the so-called "first-generation" avatar mice). The implants can be at the same location where the tumor was formed in the patient, in which case are known as orthotopic xenografts or, most commonly, at a different location, generally subcutaneous, in which case are called heterotopic xenografts. [10]
If necessary, the tumors from the first-generation avatar mice can be extracted, divided into pieces, and implanted again in multiple avatar mice ("second generation"). This process can be repeated several times to obtain a large number of avatar mice from a single patient. In general, 3–4 generations are needed to obtain enough avatar mice from a single patient.
Once the desired number of avatar mice has been achieved, the mice are treated with the several available options of chemotherapy (single agents or combined agents). The response of the tumors in the avatar mice to the various chemotherapeutic regimens is examined and the most efficient one is chosen.
The whole process usually takes several months. If the tumor of the patient recurs, then the oncologist can decide which chemotherapeutic treatment to apply based on the response of the [11] avatar mice that carried the original tumor of the patient.
The therapeutic benefits of the avatar mice have been demonstrated in pilot studies by Dr. Manuel Hidalgo with pancreatic cancer patients as well as with other cancers. [1] [12]
Transcatheter arterial chemoembolization (TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.
Azacitidine, sold under the brand name Vidaza among others, is a medication used for the treatment of myelodysplastic syndrome, myeloid leukemia, and juvenile myelomonocytic leukemia. It is a chemical analog of cytidine, a nucleoside in DNA and RNA. Azacitidine and its deoxy derivative, decitabine were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.
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Lewis lung carcinoma is a hypermutated Kras/Nras–mutant cancer with extensive regional mutation clusters in its genome. A tumor that spontaneously developed as an epidermoid carcinoma in the lung of a C57BL mouse. It was discovered in 1951 by Dr. Margaret Lewis of the Wistar Institute and became one of the first transplantable tumors.
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Champions Oncology is an American technology company that develops mouse avatars. Called TumorGrafts, they are used to test a panel of chemotherapy regimens, targeted therapies and monoclonal antibodies to identify potential therapeutic options for cancer patients. The company was founded in 2007 by David Sidransky, M.D., a Johns Hopkins University oncologist.
Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. It is a form of xenotransplantation. PDX models are used to create an environment that allows for the continued growth of cancer after its removal from a patient. In this way, tumor growth can be monitored in the laboratory, including in response to potential therapeutic options. Cohorts of PDX models can be used to determine the therapeutic efficiency of a therapy against particular types of cancer, or a PDX model from a specific patient can be tested against a range of therapies in a 'personalized oncology' approach.
Manuel Hidalgo Medina is an oncologist. He is director of the Leon V. and Marilyn L. Rosenberg Clinical Cancer Center at Beth Israel Deaconess Medical Center in Boston, Massachusetts, in the United States; he also heads its hematology/oncology division. He specializes in pancreatic cancer. His research has included development of anti-cancer drugs such as erlotinib, nab-paclitaxel and temsirolimus, and the development of patient-derived tumor xenograft models.
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The laboratory mouse has been instrumental in investigating the genetics of human disease, including cancer, for over 110 years. The laboratory mouse has physiology and genetic characteristics very similar to humans providing powerful models for investigation of the genetic characteristics of disease.
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