Discovery of Chemoresistance Biomarkers and Chemosensitizing Compounds through Combined Characterization of Genomics, Transcriptomics, and Bioinformatics

Worldwide, around 12.7 million cancers are diagnosed and 7.6 million people die of cancer each year. Cisplatin is the most commonly used chemotherapeutic drug for the treatment of tumors, such as ovarian, head and neck, esophageal, lung, bladder, cervical, and testicular cancers. Patients are highly responsive to initial treatment, but at advanced stage usually suffer from recurrence or metastasis due to cisplatin resistance. Therefore, a better understanding of the molecular mechanisms of cisplatin resistance could improve the efficacy of chemotherapy. The aim of this study is to identify aberrations in cisplatin resistance genes to serve as diagnostic or therapeutic targets and potential cisplatin sensitizers to reduce therapeutic resistance. The concept of this study is to integrate datasets of the disease (cancer cells exhibiting cisplatin resistance), genes (genes which regulate cisplatin resistance), and drugs (known compounds) to identify potential novel candidate therapeutic targets and drugs. The experimental designs of this study are as follows: (1) establishment of cisplatin-resistant cells and cisplatin-related cancer stem cells, (2) establishment and integration of cisplatin genomic and transcriptional signatures, (3) identification of therapeutic targets and networks pathways through integrating bioinformatic analysis, (4) identification of potential drugs to reverse cisplatin resistance through Connectivity Map (Cmap) analysis, and (5) validation of candidate target genes or drugs using cellular and animal models.