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Headshots of Jen Jen Yeh and Gary Johnson
UNC Lineberger’s Jen Jen Yeh, MD, and Gary Johnson, PhD.

The National Cancer Institute has awarded a five-year, $3.2 million R01 research grant to UNC Lineberger’s Jen Jen Yeh, MD, and Gary Johnson, PhD, for their project entitled, “Targeting EGFR for basal subtype cancer.” The grant will support the first metastatic pancreatic cancer trial in the country to evaluate whether selecting treatment by tumor subtype will help patients match to more effective first-line therapies. A corresponding clinical trial, known as PANGEA, should open to accrual in summer 2024.

The multidisciplinary team, consisting of translational researchers, kinome experts, and medical oncologists in the Pancreatic Cancer Center of Excellence (PCCE), hopes to determine if epidermal growth factor (EGFR) inhibitors can be repurposed for patients with basal subtype tumors. They will leverage a transformative high-sensitivity method of defining the kinome in low-input samples such as biopsies to identify targeted approaches for these tumors that are especially tricky to treat.

Basal tumors, which comprise less than 20 percent of pancreatic ductal adenocarcinoma (PDAC), are known to resist first-line chemotherapy, and patients with basal subtype tumors have significantly worse rates of survival than those with classical tumors. However, basal patients who receive anti-EGFR therapy have been shown to benefit from EGFR inhibitor therapy, whereas classical patients do not—likely due to higher EGFR kinase expression in basal tumors.

“Our hope is that targeting subtype-specific kinases will be key to promising precision oncology approaches for kinase inhibitors in PDAC,” said Yeh, Director of the PCCE and professor of surgery and pharmacology at the UNC School of Medicine. “Tumor subtyping could unlock new doors in first-line pancreatic cancer treatment, and this project is another important step toward realizing that potential.”

—Tyler Rice, UNC Lineberger Pancreatic Cancer Center of Excellence