Rosa Barreira da Silva’s fascination with biology began decades ago, in the town of Modivas, Portugal, population 1,800. Standing among the tomato vines and pea pods in her parents’ garden, she was fascinated by how each plant adapted to the region’s dramatic seasonal changes. That interest in how things work carried her into science, through a Ph.D. program, and now to a job at Genentech probing one of biology’s most complicated subjects: the human immune system.
Over the past few years, cancer immunotherapies have provided unprecedented benefits to some patients, but remain beguilingly ineffective for most others. In search of an answer, Barreira da Silva delved into how cancer interacts with the body’s natural defenses.
“This is the great thing about the work, because once you have more insight about how a pathway works, you tackle one of the biggest hurdles in cancer immunology.”
It began with a clinical observation: Patients who didn’t benefit from immunotherapy had elevated levels of what are called chemokines, proteins emitted by tumors that would normally signal to the immune system that something was amiss. Barreira da Silva discovered an enzyme called DPP4 was interrupting the normal process, modifying the cancer proteins in a way that shielded them from the immune system and allowed tumors to grow unbothered.
As it happens, there are widely available drugs that block DPP4, approved by the FDA to treat type 2 diabetes by lowering blood sugar. So to test her theory, Barreira da Silva put DPP4 inhibitors to work in cancer-afflicted mice. The results, published in Nature last year, affirmed her hunch: By keeping the enzyme at bay, chemokines set off alarm bells in the immune system, which attracted cancer-killing cells to the site of the malignancy.
The next step, Barreira da Silva said, is to apply that discovery to the latticework of knowledge about how different patients’ immune systems respond to cancer. Some treatments work by activating immune cells; others are designed to disable cancer’s defenses. Adding DPP4 into the mix creates yet another avenue to tweak the immune system and, potentially, save lives.
“This is the great thing about the work, because once you have more insight about how a pathway works, you tackle one of the biggest hurdles in cancer immunology, which is how do we define the patients who would benefit from this medicine?” Barreira da Silva said.
— Damian Garde