TAILIEUCHUNG - Transcription factor network analysis based on single cell RNA-seq identifies that Trichostatin-a reverses docetaxel resistance in prostate Cancer

Overcoming drug resistance is critical for increasing the survival rate of prostate cancer (PCa). Doc‑ etaxel is the first cytotoxic chemotherapeutical approved for treatment of PCa. However, 99% of PCa patients will develop resistance to docetaxel within 3 years. Understanding how resistance arises is important to increasing PCa survival. | Schnepp et al. BMC Cancer 2021 21 1316 https s12885-021-09048-0 RESEARCH Open Access Transcription factor network analysis based on single cell RNA-seq identifies that Trichostatin-a reverses docetaxel resistance in prostate Cancer Patricia M. Schnepp1 Aqila Ahmed1 June Escara Wilke1 Jinlu Dai1 Greg Shelley1 Jill Keller1 2 Atsushi Mizokami3 and Evan T. Keller1 2 4 5 Abstract Background Overcoming drug resistance is critical for increasing the survival rate of prostate cancer PCa . Doc etaxel is the first cytotoxic chemotherapeutical approved for treatment of PCa. However 99 of PCa patients will develop resistance to docetaxel within 3 years. Understanding how resistance arises is important to increasing PCa survival. Methods In this study we modeled docetaxel resistance using two PCa cell lines DU145 and PC3. Using the Pass ing Attributes between Networks for Data Assimilation PANDA method to model transcription factor TF activity networks in both sensitive and resistant variants of the two cell lines. We identified edges and nodes shared by both PCa cell lines that composed a shared TF network that modeled changes which occur during acquisition of docetaxel resistance in PCa. We subjected the shared TF network to connectivity map analysis CMAP to identify potential drugs that could disrupt the resistant networks. We validated the candidate drug in combination with docetaxel to treat docetaxel-resistant PCa in both in vitro and in vivo models. Results In the final shared TF network 10 TF nodes were identified as the main nodes for the development of docetaxel resistance. CMAP analysis of the shared TF network identified trichostatin A TSA as a candidate adjuvant to reverse docetaxel resistance. In cell lines the addition of TSA to docetaxel enhanced cytotoxicity of docetaxel resistant PCa cells with an associated reduction of the IC50 of docetaxel on the resistant cells. In the PCa mouse model combi nation of TSA and docetaxel reduced tumor growth

• Y khoa - Dược
• BMC Cancer
• Docetaxel resistance prostate cancer
• Single cell RNA sequencing
• PANDA method
• Transcription factor network analysis
• Cancer patient pathways
• Colorectal cancer
• Lung cancer
• Breast cancer
• Prostate cancer
• Ovarian cancer
• Cancer detection
• Ovarian cancer symptoms
• Ovarian cancer signs
• Ovarian cancer tests
• Cancer biomarkers
• Pediatric cancer
• Familial cancer predisposition
• Hereditary cancer syndrome
• Genetic cancer susceptibility
• Advanced cancer
• Biliary tract cancer
• Multimodal intervention
• Pancreatic cancer
• Physical activity
• Breast cancer screening
• Familial breast cancer
• Young breast cancer survivors
• High risk relatives
• Randomized trial
• Childhood cancer
• Childhood cancer survivor
• Thyroid cancer screening
• Secondary cancer
• Cancer screening
• Community awareness
• Cancer education
• Cervical cancer
• Prior cancer
• Cancer survivors
• Cancer registry
• Second cancer
• Surgical oncology
• Cancer imaging
• Radiation oncologists
• Medical oncologists
• Oesophagogastric cancer
• Liver cancer
• Hepatobiliary cancer
• Multidisciplinary rehabilitation
• EGFR mutation
• Family history of cancer
• Inherited susceptibility
• Cancer predisposition genes
• Lung cancer aetiology
• Cancer stem cells
• Oct4 overexpressing lung cancer
• Human lung cancer xenograft model
• Disease free survivals
• Cancer hallmarks
• Cancer genesis
• Defiant disease
• Mutational signature
• Cancer diagnosis
• Cancer genomics
• Molecular medicine
• Whole genome sequencing
• Cancer susceptibility gene
• Breast cancer prognosis
• Next generation sequencing
• Quality of care
• Quality indicators
• Shifting cancer care
• German cancer society
• Colorectal cancer screening
• Stomach cancer screening
• Lung cancer survivor
• Physician recommendation
• Total number of lymph nodes
• Lymph node ratio
• Left colon cancer
• Right colon cancer
• Overall survival
• Cumulative incidence
• Esophageal cancer
• Head and neck cancer
• Metachronous cancer
• Young onset
• Reproductive cancer
• Risk factor
• Early detection of cancer
• Gastric cancer incidence
• Population based specialized registry
• Gastric cancer survival
• Gastric cancer clinical characteristics
• Gastric cancer pathological characteristics
• Lung Cancer Screening
• Racial disparities
• Lung Cancer diagnosis
• Screening adherence
• Second primary colorectal cancer
• Standardized incidence ratio
• Left sided colon cancer
• Right sided colon cancer
• Quality of cancer care
• Population based study