Hepatocellular carcinoma (HCC), the main cause of liver cancer-related death, is one of the main cancers in terms of incidence and mortality. However, HCC is difficult to target and develops strong drug resistance. Therefore, a new treatment strategy is urgently needed. The clinical application of the concept of synthetic lethality in recent years provides a new therapeutic direction for the accurate treatment of HCC. Here, we introduce the concept of synthetic lethality, the screening used to study synthetic lethality, and the identified and potential genetic interactions that induce synthetic lethality in HCC. In addition, we propose opportunities and challenges for translating synthetic lethal interactions to the clinical treatment of HCC.
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http://dx.doi.org/10.1016/j.canlet.2020.02.016 | DOI Listing |
Essential genes, estimated at approximately 20% of the genome, are broadly expressed and required for reproductive success. They are difficult to study, as interfering with their function leads to premature death. Transcription is one of the essential functions of life, and the multi-protein Mediator complex coordinates the regulation of gene expression at nearly every eukaryotic promoter.
View Article and Find Full Text PDFExp Mol Med
January 2025
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
FHIT is a fragile site tumor suppressor that is primarily inactivated upon tobacco smoking. FHIT loss is frequently observed in lung cancer, making it an important biomarker for the development of targeted therapy for lung cancer. Here, we report that inhibitors of glycogen synthase kinase 3 beta (GSK3β) and the homologous recombination DNA repair (HRR) pathway are synthetic lethal with FHIT loss in lung cancer.
View Article and Find Full Text PDFTransl Oncol
January 2025
Tango Therapeutics, Tango Therapeutics, 201 Brookline Avenue, Boston, 02215, MA, United States.
TNG908 is a clinical stage PRMT5 inhibitor with an MTA-cooperative binding mechanism designed to leverage the synthetic lethal interaction between PRMT5 inhibition and MTAP deletion. MTAP deletion occurs in 10-15 % of all human cancer representing multiple histologies. MTA is a negative regulator of PRMT5 that accumulates as a result of MTAP deletion.
View Article and Find Full Text PDFNat Commun
January 2025
Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Long noncoding RNAs known as roX (RNA on the X) are crucial for male development in Drosophila, as their loss leads to male lethality from the late larval stages. While roX RNAs are recognized for their role in sex-chromosome dosage compensation, ensuring balanced expression of X-linked genes in both sexes, their potential influence on autosomal gene regulation remains unexplored. Here, using an integrative multi-omics approach, we show that roX RNAs not only govern the X chromosome but also target genes on autosomes that lack male-specific lethal (MSL) complex occupancy, together with Polycomb repressive complexes (PRCs).
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
December 2024
Department of Otolaryngology-Head Neck Surgery, Keio University School of Medicine, Japan.
The DNA damage response (DDR) is an essential mechanism for maintaining genomic stability. Although DDR-targeted therapeutic strategies are being developed in several familial cancers, evaluation of their utility in head and neck squamous cell cancer (HNSCC) is lagging. This review briefly summarizes the mechanisms of DDR and the current knowledge on discovering DDR-related predictive biomarkers in HNSCC.
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