Researchers Discover How Promising New Anti-Cancer Drug Class Works

Cancer drug called nutlins activate the P53 gene to trigger blood cancer cell death instead of temporarily suppressing the disease.

Researchers from the Walter and Eliza Hall Institute of Medical Research have found how a promising anti-drug cancer works.

This new drug class called nutlins have the ability to stop cancer growth by activating the P53 gene — a natural cancer suppressing mechanism – while simultaneously avoiding some of the damaging effects that chemotherapy can have.

However, in earlier clinical trials for blood cancers, it was not clear whether nutlins killed the cancerous cells or just temporarily suppressed them.

The study, published in Cell Reports, showed that nutlins activated the P53 gene to trigger blood cancer cell death instead of just temporarily suppressing the disease. This was identified through the presence of the protein PUMA.

"Our findings will help identify which patients are most likely to benefit from nutlins and which types of cancers are most likely to respond to nutlins as a treatment," said clinical hematologist at Royal Melbourne Hospital, Brandon Aubrey. "Understanding in detail how the drugs work will help in the design of better clinical trials and bring the world closer to more precise and personalized medical treatments for cancer."

Prior research has shown that P53 was a natural “guardian” of the healthy cells and was a barrier to developing cancerous cells.

"When functioning properly, P53 is activated in response to early cancerous changes in the cell," said Professor Andreas Strasser. "P53 acts by either halting the cell while repairs are made or by forcing the cell to die if it cannot be repaired. Without the 'help' of P53, a damaged cell can be allowed to multiply, leading to cancer development. P53 lies dormant in many types of cancer -- that do not have mutations in P53 -- and the nutlins work through re-awakening its activity."

Researchers believe that identifying what nutlins were was critical to helping develop future treatments.

"By understanding how nutlins are killing cancer cells, we can begin to formulate their best possible use, including choosing the best partner drugs to combine the nutlins with," Strasser said.