Researchers solve mystery about action of new class of cancer drug
A team from the Walter and Eliza Hall Institute (Melbourne, Australia) have resolved a mystery about the action of a novel class of anti-cancer drugs, nutlins, with potential implications for future cancer treatments.
Nutlins are a class of therapeutics currently in early-stage clinical trials for treating blood cancers, but it has been until now unknown whether they act by killing cancerous cells or by suppressing them temporarily. A team of researchers from the Walter and Eliza Hall Institute (Melbourne, Australia) have discovered the answer: nutlins act by forcing cancer cells to self-destruct.
Nutlins have sparked interest worldwide for their ability to halt cancer growth by activating the body’s natural cancer-suppressing gene, P53, without some of the damaging effects of chemotherapy. This research backs the evidence that nutlins are a promising new treatment, while also providing important information for patient care.
The research reveals that nutlins activate P53 to trigger programmed cell death of blood cancer cells, through the presence of a protein called PUMA. Brandon Aubrey, one of the study’s authors, explained: "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.”
Aubrey continued, "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 personalised medical treatments for cancer."
Andreas Strasser, another member of the research team, added that previous research around P53 indicated that the gene was a guardian of healthy cells in the body and acted as a barrier to developing cancer."When functioning properly, P53 is activated in response to early cancerous changes in the cell," Strasser elaborated. "P53 acts by either halting the cell while repairs are made or by forcing the cell to die if it cannot be repaired.”
Strasser added: "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."
Strasser concluded that the team’s research was a critical step towards developing more sophisticated cancer treatments. In summation, he stated: "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.”
Valente LJ, Aubrey BJ, Herold MJ et al. Therapeutic response to non-genotoxic activation of p53 by Nutlin3a is driven by PUMA-mediated apoptosis in lymphoma cells. Cell Reports doi: 10.1016/j.celrep.2016.01.059 (2016) (Epub ahead of print); https://www.sciencedaily.com/releases/2016/02/160219100329.htm