Dr. Deepak Saxena Awarded Department of Defense Grant to Target the Microbiome in Treating Pancreatic Cancer
Pancreatic cancer is the fourth leading cause of cancer deaths and is notoriously aggressive and difficult to treat. The most common form, pancreatic ductal adenocarcinoma (PDA), is usually fatal within two years.
Immunotherapy—an increasingly important treatment option that fights cancer by activating the immune system—thus far has had little success in pancreatic cancer. However, researchers at NYU College of Dentistry and NYU Grossman School of Medicine have shown that targeting the pancreas’ microbiome—the community of microorganisms including bacteria—may be the key to enabling immunotherapy to treat PDA.
To continue this research, NYU College of Dentistry and NYU Grossman School of Medicine have received a Translational Team Science Award from the Department of Defense totaling $1.6 million. The four-year grant, which began September 30, covers three synergistic projects, one of which (W81XWH-19-1-0605) is led by Deepak Saxena, PhD, professor of basic science and craniofacial biology at NYU College of Dentistry.
Saxena and his colleagues have shown that the microbiome plays a role in promoting the development of PDA and in reducing its response to therapy. The team's 2018 study published in Cancer Discovery found that the microbiome of a cancerous pancreas is expanded by more than a thousand fold compared with a normal pancreas. In addition, the bacteria that are more abundant in PDA help to shift macrophages, the key immune cells in the pancreas, into immune suppression. In their study, eliminating bacteria using antibiotics restored the ability of immune cells to recognize cancer cells, slowed tumor growth, and reduced the number of cancer cells present by 50 percent in mice with PDA.
"Based on these data, the microbiome is an attractive target in the treatment of pancreatic cancer," said Saxena. "Our overarching hypothesis is that targeting pathogenic bacteria using antibiotics will augment innate and adaptive immunity in patients with pancreatic cancer and enable immunotherapy to be successful."
The researchers will develop and test the efficacy of specific antibiotic and probiotic cocktails in mouse models of PDA, tumors removed from patients with PDA, and 3D models of human PDA. They will then translate the knowledge they gain from these experiments into a Phase I clinical trial testing the safety and efficacy of antibiotics in combination with checkpoint-receptor based immunotherapy in patients with pancreatic cancer.
The project is a collaboration among three principal investigators: Saxena, a microbiologist who has defined the PDA microbiome; NYU Langone's George Miller, MD, a clinician-scientist with a successful track-record investigating the inflammation/cancer paradigm in PDA; and NYU Langone’s Deirdre Cohen, MD, an accomplished clinical trialist in gastrointestinal oncology.