Press Release: New Research may Lead to Breakthroughs in Combating Cancer Drug Resistances

Posted on October 20, 2021 by Admin

New research has revealed the differences in mechanism behind cancer’s resistance to the major class of anti-cancer drugs known as nucleoside analogues.

Nucleosides are molecules containing the genomic information that can be chemically modified into so-called nucleoside analogues to cause them to inhibit DNA formation in cancer cells, causing the cells to die. However, the presence of the enzyme SAMHD1 aids the cancer’s resistance to this treatment.

This new understanding, provided by the University of Kent’s School of Biosciences and the Institute of Medical Virology at Goethe-University, may lead to further breakthroughs in combatting resistances to anti-cancer therapies.

Researchers, supported by the Frankfurter Stiftung für krebskranke Kinder, investigated the drug candidate CNDAC, with hopes it would prevent SAMHD1’s involvement in the cancer’s resistance to treatments.

The study confirmed that CNDAC does not inhibit SAMHD1 and so would not support nucleoside analogue treatments.

However, the research revealed differences in the resistance mechanisms between leukemia cells immediately unresponsive to treatment and those that developed resistance over time.

In cells immediately unresponsive to treatment, resistance was found to be due to high levels of SAMHD1 inactivating the nucleoside analogues. In contrast, cells that had developed resistance were found to include the enzyme DCK, which is involved in the activation of nucleoside analogues.

Notably, developed resistance to nucleoside analogue treatments resulted in cross-resistance to other closely related nucleoside analogues activated by the same DCK enzyme. This profound revelation may help inform further treatments for cancer in the future.