Disruption of RNA Splicing Increases Vulnerability of Cells to DNA-PK Inhibitors.

DNA-dependent protein kinase (DNA-PK) is a key effector of non-homologous end joining (NHEJ)-mediated double-strand break (DSB) repair. Since its identification, a substantial body of evidence has demonstrated that DNA-PK is frequently overexpressed in cancer, plays a critical role in tumor development and progression, and is associated with poor prognosis in cancer patients. Recent studies have also uncovered novel functions of DNA-PK, shifting the paradigm of the role of DNA-PK in oncogenesis and renewing interest in targeting DNA-PK for cancer therapy.

The Origin of Genetic Code and Translation in the Framework of Current Concepts on the Origin of Life.

The origin of genetic code and translation system is probably the central and most difficult problem in the investigations on the origin of life and one of the most complex problems in the evolutionary biology in general. There are multiple hypotheses on the emergence and development of existing genetic systems that propose the mechanisms for the origin and early evolution of genetic code, as well as for the emergence of replication and translation. Here, we discuss the most well-known of these hypotheses, although none of them provides a description of the early evolution of genetic systems without gaps and assumptions.

Possibility for Transcriptional Targeting of Cancer-Associated Fibroblasts-Limitations and Opportunities.

Cancer-associated fibroblasts (CAF) are attractive therapeutic targets in the tumor microenvironment. The possibility of using CAFs as a source of therapeutic molecules is a challenging approach in gene therapy. This requires transcriptional targeting of transgene expression by cis-regulatory elements (CRE).

PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma.

In cancer biology, metastasizing is one of the most poorly studied processes. Pancreatic ductal adenocarcinoma (PDAC) is characterized by early metastasis, which is the leading cause of death. The PDX1 protein is crucial for the development of cancer, and its low levels are characteristic of the most aggressive PDAC tumors.