CCDC88C‐FLT3 gene fusion in CD34‐positive haematopoietic stem and multilineage cells in myeloid/lymphoid neoplasm with eosinophilia

Prostate cancer (PCa) is the most frequent cancer in men. The evolution from local PCa to castration-resistant PCa, an end-stage of disease, is often associated with changes in genes such as p53, androgen receptor, PTEN, and ETS gene fusion products. Evidence is accumulating that repurposing of metformin (MET) and valproic acid (VPA) either when used alone, or in combination, with another therapy, could potentially play a role in slowing down PCa progression. This review provides an overview of the application of MET and VPA, both alone and in combination with other drugs for PCa treatment, correlates the responses to these drugs with common molecular changes in PCa, and then describes the potential for combined MET and VPA as a systemic therapy for prostate cancer, based on potential interacting mechanisms.

Download Full-text

A New Type of Fusion Analysis Applicable to Many Organisms: Protein Fusions to the URA3 Gene of Yeast

Genetics ◽

10.1093/genetics/117.1.5 ◽

1987 ◽

Vol 117 (1) ◽

pp. 5-12

Author(s):

Eric Alani ◽

Nancy Kleckner

Keyword(s):

Gene Fusion ◽

Enzyme Assay ◽

Decarboxylase Activity ◽

Lacz Gene ◽

Coding Region ◽

Ura3 Gene ◽

Promoter Sequences ◽

E Coli ◽

New Type ◽

Fusion Analysis

ABSTRACT We have made constructs that join the promoter sequences and a portion of the coding region of the Saccharomyces cerevisiae HIS4 and GAL1 genes and the E. coli lacZ gene to the sixth codon of the S. cerevisiae URA3 gene (encodes orotidine-5′-phosphate (OMP) decarboxylase) to form three in frame protein fusions. In each case the fusion protein has OMP decarboxylase activity as assayed by complementation tests and this activity is properly regulated. A convenient cassette consisting of the URA3 segment plus some immediately proximal amino acids of HIS4C is available for making URA3 fusions to other proteins of interest. URA3 fusions offer several advantages over other systems for gene fusion analysis: the URA3 specified protein is small and cytosolic; genetic selections exist to identify mutants with either increased or decreased URA3 function in both yeast (S. cerevisiae and Schizosaccharomyces pombe) and bacteria (Escherichia coli and Salmonella typhimurium); and a sensitive OMP decarboxylase enzyme assay is available. Also, OMP decarboxylase activity is present in mammals, Drosophila and plants, so URA3 fusions may eventually be applicable in these other organisms as well.

Download Full-text

FGFR-TKI resistance in cancer: current status and perspectives

Journal of Hematology & Oncology ◽

10.1186/s13045-021-01040-2 ◽

2021 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Sitong Yue ◽

Yukun Li ◽

Xiaojuan Chen ◽

Juan Wang ◽

Meixiang Li ◽

...

Keyword(s):

Gene Fusion ◽

Kinase Inhibitors ◽

Current Status ◽

Great Success ◽

Fibroblast Growth Factor Receptors ◽

Pathway Activation ◽

Tki Resistance ◽

Covalent Inhibitors ◽

And Migration ◽

Dual Target

AbstractFibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment.

Download Full-text