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UPFRONT: Cancer’s Dead End
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Cancer’s Dead End by Christie Aschwanden
There is a way to restore p53’s tumor-suppressing prowess.
At first glance, the tumor-suppressor gene p53 would seem like an ideal weapon against cancer. It puts the brakes on cancer progression and is impaired in about half of human tumors.
In mouse models of cancer, HHMI investigators Tyler Jacks and Scott Lowe restored p53 activity in tumors and the tumors regressed. However, p53 activation kills some cancer cells, but not others, and no one knows why. HHMI early career scientist Joaquín Espinosa has set his sights on finding an answer, and with it, a strategy for making p53-based therapies effective. It’s a goal he’s pursued with relentless passion.
“He’s an extremely creative thinker,” says former HHMI President Thomas Cech, who is an HHMI investigator and colleague of Espinosa’s at the University of Colorado at Boulder. Where a traditional approach might focus entirely on the p53 gene itself, Espinosa has adopted a broader and far more ambitious target—he aims to inventory all the genes and pathways that govern how cells react to p53 activation.
Espinosa’s approach grew from his realization that if you want to harness p53’s tumor-squelching effects, you also need to block the myriad pathways that tumors use to circumvent p53’s killing orders. Espinosa sought to identify all of the p53-disarming pathways and the genes that control them with a technique called functional genomics. “This is a very new technology which allows us to interrogate the function of every gene in the human genome as it relates to p53,” Espinosa says. “With functional genomics, we can ask—which genes influence the programmed cell death mediated by p53?”
To do functional genomics requires expensive equipment and huge libraries of costly reagents, and only a few such facilities exist in the world. Espinosa wanted one at the University of Colorado at Boulder. He had a vision for a functional genomics facility in Colorado that would not only advance his own research, but also put his colleagues at the forefront of biomedical research. “Joaquín enjoys doing things for the benefit of the scientific community,” Cech says. “He’s more than a team player, he’s an instigator of teamwork.”