Date of Award

Spring 2019

Document Type

Honors Thesis

Department/Major

Basic Biomedical Science

First Advisor

Dr. Jianning Tao

Second Advisor

Ashley VanCleave

Third Advisor

Dr. Fang Fang

Keywords

Osteosarcoma, Rapamycin, mTORC1, Metastasis

Abstract

Osteosarcoma (OS) is the predominant form of primary malignant bone cancer and is most commonly found in children and adolescents. OS is associated with high mortality rates and poor prognosis for the majority of patients [1]. Within the last few decades, there has been little to no improvement in patient outcome. Current treatment methods include surgical excision of the tumor alongside chemotherapy. However, high rates of metastasis still persist, which is considerably more difficult to target with chemotherapy or to remove by surgery [2].

Thanks to recent advances in molecular genetics and medicine, we can better understand OS and the properties of the cancer in order to develop an improved treatment plan. We examined a novel Patient Derived Xenograft (PDX) cell line, OS-33. While little is known about OS-33, preliminary data indicates sensitivity to the drug rapamycin, which is suggested to inhibit the mammalian target of rapamycin complex 1 (mTORC1) pathway [3]. The mTORC1 pathway is upregulated in many OS patients, which highlights this pathway as a new and promising therapeutic target [3]. The inhibition of mTORC1 signaling by rapamycin was studied to determine how it suppresses cell migration, invasion, proliferation, and stem cell differentiation in the OS-33 cell line. This study underlines the importance of the mTORC1 signaling pathway and provides evidence for potential drugs which target OS.

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