Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover novel regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.
Project description:PARP inhibitors (PARPi) have demonstrated efficacy in treating human cancers with BRCA1 or BRCA2 gene mutations, which are present in only a small portion of breast, ovarian, prostate, and pancreatic cancers. In this study, we discovered that OFD1 is highly expressed in pancreatic cancer and is associated with a poor prognosis. Through screening an FDA-approved drug library, we found that OFD1 knockdown synergizes most effectively with PARPi for the treatment of pancreatic cancer cells. To explore the mechanism of OFD1 knockdown and PARP inhibitor-induced synthetic lethality, we knocked down OFD1 in three pancreatic cancer cell lines and performed RNA sequencing analysis of the whole genome to investigate the mechanisms underlying OFD1 inhibition and PARP inhibitor-induced synthetic lethality. In summary, our research will provide insights into the role of OFD1 in pancreatic cancer by revealing changes in the whole-genome expression profile and the underlying mechanisms.
Project description:To identify differentially expressed genes by miRNAs transfection in human cancer, several cell lines (colon cancer and pancreatic cancer) were subjected to Agilent whole genome microarrays.
Project description:To identify differentially expressed genes by anti cancer treatments (siRNAs) in human cancer, several cell lines (lung cancer, breast cancer and pancreatic cancer) were subjected to Agilent whole genome microarrays.
Project description:To identify differentially expressed genes by anti cancer treatments (siRNAs and miRNAs) in human cancer, several cell lines (esophagus cancer, renal cell carcinoma and pancreatic cancer) were subjected to Agilent whole genome microarrays.
Project description:In order to better study the differences between pancreatic cancer patients' tumor tissues and their adjacent tissues, we compared chromatin accessibility of pancreatic cancer tumor tissues and adjacent tissues of the same patient from the whole genome, in an effort to find meaningful research targets related to pancreatic cancer patients
Project description:To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (pancreatic cancer, esophageal cancer and lung squamous cell carcinoma) were subjected to Agilent whole genome microarrays.