New Class Of Drugs Make Cancer Cells "Sleep" Without Damaging Surrounding Cells' DNA

Lymphoma cells under a microscope. Rather than killing these cells, a new treatment puts them to sleep, potentially avoiding much collateral damage. CoRus13 CC by 4.0

Rather than undertaking the dangerous task of killing the monster Cerberus, Orpheus (and more recently Professor Quirrell) lulled it to sleep with music. Scientists have followed this example in tackling the modern monster, cancer. By making cells dormant they’re avoiding the casualties involved in putting them to death.

KAT6A and KAT6B are proteins that control embryonic development, and also induce cancer. Indeed, the gene for KAT6A is the 12th most frequently amplified gene in cancer cells.

Dr Tim Thomas and Dr Anne Voss of the Walter and Eliza Hall Institute, Melbourne, have spent years investigating KAT6 proteins for cancer treatments. “Early on, we discovered that genetically depleting KAT6A quadrupled the life expectancy in animal models of blood cancers called lymphoma,” Thomas said in a statement.

Blocking or removing KAT6 proteins is a lot more realistic than genetically modifying cancer patients, with many theoretical advantages over existing cancer treatments. Chemotherapy and radiotherapy damage cells’ DNA. While more harmful to cancer cells than healthy cells, there is plenty of damage to go around, particularly for fast-dividing cells like those lining the gut.

Shutting down KAT6 kills nothing, instead stopping cancer cells dividing, which Voss and Thomas call putting them to sleep. “The technical term is cell senescence. The cells are not dead, but they can no longer divide and proliferate. Without this ability, the cancer cells are effectively stopped in their tracks.” said Voss.

Identifying target proteins is only part of the problem, however. “We screened a large library of compounds – half a million – to identify one that has activity against KAT6A and then tried to change it to make it suitable,” Thomas told IFLScience.

An early version, known as WM-8014 binds to a mammalian blood plasma protein, rendering it effective. However, the team demonstrated WM-8014's capacity to control cancer in zebrafish, and then worked to create a modified version that might work in mammals. In their study published in Nature, Thomas and Voss describe the use of their adapted molecule WM-1119 to eliminate mice lymphomas, although quite high doses were needed.

Thomas explained to IFLScience that KAT6A blocking is expected to work against a subset of cancers in a wide range of organs, with genomics making it increasingly easy to identify the patients who are likely to respond well. However, further modifications will be needed before testing in humans can begin, the risk of long-lasting side effects appears low.

Although a treatment that leaves cancer cells sleeping may sound alarming, as if the slightest disturbance might wake them, Thomas anticipates that “The body will eventually recognize them as abnormal and clear the cells.”

Blocking the body’s proteins can be fraught, since it interferes with their normal function, but Thomas told IFLScience KAT6A appears unnecessary in adults.

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