REPURPOSING OF KNOWN DRUGS AS POTENTIAL THERAPEUTICS FOR CANCER IMMUNOTHERAPY FOR PATIENTS WITH SOLID TUMORS
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Mingjia Fan, Moustafa Gabr
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For several decades treatment of advanced cancer has been challenged by lack of reliable therapeutic options. Patients with metastatic tumors that were not surgically resectable had to depend on chemotherapy, which is commonly associated with severe adverse events as well as high rates of relapse. As the understanding of immune system and immune surveillance grew, the idea of utilizing immune cells to eliminate cancer gained significance and various strategies to activate immune response were developed.
Tumor cells form immune escape and subsequently obtain unlimited proliferation ability due to the abnormal immune surveillance mediated by immune checkpoints. Negative immune checkpoints, such as programmed cell death protein 1 (PD-1), are regulators of human immune system that downregulate T-cell activation and hinder the ability of the immune system to attack cancer cells. FDA-approved monoclonal antibodies (mAbs) against negative immune checkpoints have revealed remarkable clinical success in different malignancies. However, there are currently no small molecules clinically approved based on targeting immune checkpoints. The aim of this project is to identify FDA-approved drugs that can be potentially used to target immune checkpoints and inhibit their function. The approach will be based on a computational study by investigating the ability of a library of known drugs to interact with the crystal structure of PD-1. This work would potentially enable the development of small molecules for early cancer diagnosis and personalized cancer immunotherapy.
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Authors
Mingjia Fan, Moustafa Gabr
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