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New class of drug puts cancer cells to sleep

6 August 2018
Appeared in BioNews 961

Australian researchers have developed a new kind of anti-cancer drug, which halted cancer cells in their tracks in mice.

Published in Nature, this new family of drugs block a trick that cancer cells use to keep growing – stopping their growth and forcing them to 'go to sleep'. As these compounds do not cause DNA damage (unlike chemotherapy and radiotherapy) the authors hope that patients receiving them would not have the usual side effects associated with more traditional cancer treatments.

'The drugs were well tolerated in our preclinical models and are very potent against tumour cells, while appearing not to adversely affect healthy cells,' said Dr Tim Thomas at the Walter and Eliza Hall Institute in Victoria, who led the work together.

The new drugs interfere with an enzyme called KAT6A, which is frequently altered in cancers, as cells which over-produce can show out-of-control growth.

KAT6A is an epigenetic regulator, chemically modifying proteins that control which sections of DNA are turned on or off. When active, KAT6A turns on sections of DNA which help cancer cells multiply; so when blocked, the cancer cells are unable to divide.

Almost a quarter of a million different compounds were originally screened to find a molecule which could block KAT6A from doing its job. The most promising candidate was then taken forward into this study, undergoing several rounds of modification by medicinal chemists to make the drug stronger and more specific.

The final chemicals produced were able to stop cancer in its tracks in several laboratory models of cancer, including lymphoma in mice.

The researchers showed how these drugs were able to get into cells and prevent KAT6A from modifying its target proteins, preventing the cancer cells from dividing – inducing a state called 'senescence'.

Importantly, these drugs did not appear to have a large effect on non-cancerous cells, decreasing the likelihood that they would cause 'off-target' side effects in patients.

'Our discovery suggests these drugs could be particularly effective as a type of consolidation therapy that delays or prevents relapse after initial treatment,' said Dr Anne Voss, also at the institute, and one of the lead authors.

She continued that 'the possibility of giving clinicians another tool that they could use to substantially delay cancer recurrence could have a big impact for patients'.

While these data are encouraging, this new family of drugs is a long way off from being tested in human patients. The tests in animal models have looked at only very short time periods; as these drugs aren’t killing cancer cells much longer experiments will be necessary to determine whether there are long term side effects, or if the cancer cells can become resistant and 'wake up'.

Australian researchers develop new drug that puts cancer cells to 'sleep' in mice
ABC News |  2 August 2018
Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth
Nature |  1 August 2018
New anti-cancer drugs put cancers to sleep…permanently
Walter and Eliza Hall Institute of Medical Research |  2 August 2018
New Class Of Drugs Make Cancer Cells 'Sleep' Without Damaging Surrounding Cells' DNA
IFLScience |  2 August 2018
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