Human leiosarcoma and non small cell lung cancer lung xenograft models

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Soft tissue sarcomas are malignant tumors that originate from fat, muscle, nerve, blood vessel, and fibrous or deep skin tissues and can occur in most parts of the body. Leiomyosarcoma (LMS) is a malignant tumor originating from smooth muscle tissue, most often the retroperitoneum, internal organs and blood vessels. While occurrence of LMS is quite rare, current therapies are limited and treatment potential for newly approved agents and novel combination regimens are largely unknown, primarily due to lack of evaluable models for each disease.

On the other hand, non small cell lung cancer (NSCLC) is more common, accounting for the majority of the 164,000 new lung cancer patients annually. NSCLC comprises three main types of cancer: squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. These histologies are often classified together because approaches to diagnosis, staging, prognosis, and treatment are similar. Patients with resectable disease may be cured by surgery or surgery with adjuvant chemotherapy. Local control can be achieved with radiation therapy in a large number of patients with unresectable disease, but cure is seen only in a small number of patients. Patients with locally advanced, unresectable disease may have long-term survival with radiation therapy combined with chemotherapy. Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy. Animal models of the disease in general, and of a particular patient's tumor, would be invaluable in identifying potentially active chemotherapeutic agents as well as personalizing treatments.

In one embodiment, a human leiomyosarcoma xenograft model is provided that is capable of stable propagation in immunodeficient mice. In a further embodiment, the model is useful for P-9857-PC determining sensitivity of tumor growth to single or combinations of chemotherapeutic agents administered to the mouse. In another embodiment, the model demonstrates specificity towards various chemotherapeutic agents and combinations thereof.

In another embodiment, a method is provided for identifying an optimal chemotherapeutic regimen for a human leiomyosarcoma tumor in a patient by the steps of (1) establishing a xenograft of the tumor in immunodeficient mice, (2) confirming the phenotypic stability of the tumor, and (3) evaluating the effect on tumor growth inhibition by at least one chemotherapeutic regimen, such as by a single agent or at least one combination of chemotherapeutic agents, wherein an effective chemotherapeutic regimen in the xenograft model identifies a regimen useful for treatment of the disease in the patient. In another embodiment, the optimal schedule and dose of chemotherapeutic agent administration is determined in the model then applied to the patient.

In another embodiment, a method is provided for assessing the effect of a composition or treatment on human leiomyosarcoma, comprising: a) providing an immune deficient mouse comprising a xenograft of human leiomyosarcoma, wherein the xenograft is allowed to grow for a sufficient time to permit the detection of a tumor; b) subjecting the mouse to the composition or treatment; and, c) determining the effect of the composition or treatment on the growth of the xenograft in the mouse. In another embodiment, the xenograft is a subcutaneous xenograft. In another embodiment, the immune deficient mouse is a nude mouse.

In another embodiment, an immunodeficient mouse is provided having a xenograft of a human leiomyosarcoma. In a further embodiment, the xenograft is subcutaneous. In another embodiment, the immunodeficient mouse is a nude mouse.

In another embodiment, a human non small cell lung cancer xenograft model is provided that is capable of stable propagation in immunodeficient mice. In a further embodiment, the model is useful for determining sensitivity of tumor growth to single or combinations of chemotherapeutic agents administered to the mouse. In another embodiment, the model demonstrates specificity towards various chemotherapeutic agents and combinations thereof.

In yet another embodiment, a method is provided for identifying an optimal chemotherapeutic regimen for a human non small cell lung cancer in a patient by the steps of (1) establishing a xenograft of P-9857-PC the tumor in immunodefϊcient mice, (2) confirming the phenotypic stability of the tumor, and (3) evaluating the effect on tumor growth inhibition by at least one chemotherapeutic regimen, such as by a single agent or at least one combination of chemotherapeutic agents, wherein an effective chemotherapeutic regimen in the xenograft model identifies a regimen useful for treatment of the disease in the patient. In another embodiment, the optimal schedule and dose of chemotherapeutic agent administration is determined in the model then applied to the patient.

In another embodiment, a method is provided for assessing the effect of a composition or treatment on human non small cell lung cancer, comprising: a) providing an immune deficient mouse comprising a xenograft of human non small cell lung cancer, wherein the xenograft is allowed to grow for a sufficient time to permit the detection of a tumor; b) subjecting the mouse to the composition or treatment; and, c) determining the effect of the composition or treatment on the growth of the xenograft in the mouse. In another embodiment, the xenograft is a subcutaneous xenograft. In another embodiment, the immune deficient mouse is a nude mouse.

In another embodiment, an immunodeficient mouse is provided having a xenograft of a human non small cell lung cancer. In a further embodiment, the xenograft is subcutaneous. In another embodiment, the immunodeficient mouse is a nude mouse.