Rapid expansion of molecular biologists’ knowledge of how cancerous cells with damaged DNA sustain a long lifespan has helped us find new aggressive ways to wipe out cancer cells such as more effective chemotherapy. One key obstacle to tackle is the fact that cancerous cells quickly become resilient to DNA-harming medications. This leads to many chemotherapy failures.
A new research just appeared in Nature Structural and Molecular Biology introduced an innovative method of dealing with death-evading cancerous cells by stripping these cells of their drug-resistance developing capabilities, more vulnerable to DNA damaging drugs hence.
Pancreatic cancer cells deficient in the expression of the human gene known as Schlafen 11 and resistant to chemotherapy (left panels) were re-sensitized to chemotherapeutic treatment (middle and right panels) by inhibiting the expression of the transfer RNA known as tRNA-Leu-TAA through specially designed antisense oligonucleotides. [Manqing Li, Michael David Lab, UC San Diego] (Genetic Engineering & Biotechnology News (GEN))
David’s Lab further found out that, similar to the transfer RNA molecules of Schlafen 11, transfer RNA molecules of several gene families involved in DNA repair systems are encoded by transfer RNA gene rich in leucine amino acid. This provides a clue for making drug-resistant cancerous cells sensitive anew by attacking the transfer RNA molecules of DNA repair genes.
The findings show that disruption of normal functions of both ATR and transfer RNA could kill the cancerous cells combined with chemotherapy even though this technique could compromise whole DNA repair system. The paper also shows the role of cellular adjustments made in levels of transfer RNAs in survival or death of a cell with damaged-DNA for the first time.
by: Jamaledin Adel
https://www.nature.com/articles/s41594-018-0142-5?_ga=2.70392784.117150651.1540857600-2063335005.1540857600
