Future scope of Pancreatic Cancer

Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumors do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable.

For many years, chemotherapeutic regimens have been the cornerstone of therapy for inoperable pancreatic adenocarcinoma (PC) (i.e., locally advanced or metastatic) and evolved as adjuvant or neoadjuvant treatment for resectable pancreatic carcinoma. Overall, however, pancreatic carcinoma shows only moderate sensitivity to chemotherapy. This is reflected by the overall dismal prognosis, that has not improved over the last years.

Pancreatic cancer spreads (metastasizes) very early during its development. In 85 percent of patients, the cancer has already spread outside of the pancreas at diagnosis. Even when the cancer is localized to the pancreas and surgical removal is possible, the majority of patients face a recurrence of their cancer. The metastasis causes these patients to eventually succumb to the disease, which is why researchers are focused on understanding the biology of metastatic pancreatic cancer.

Researchers Seek to Improve Survival by Moving Quickly from Laboratory to Patients.

The clinical trial at Wilmot Cancer Institute, planned for early in 2024, to test the drug from their laboratory discovery. Wilmot Cancer Institute will be the first institution in the U.S. to study the safety and effectiveness of the experimental drug, known as NP137, on pancreatic cancer that has spread to the liver.

NP137 is the first-in-class humanized monoclonal antibody specific to Netrin-1 which targets the V2 subdomain that is critical for binding to the Unc5 receptors. NP137 was shown to be safe in a phase I clinical trial for multiple solid organ cancers (NCT02977195) and is now being evaluated in phase II in patients with advanced gynecological cancers in a follow-up study of locally advanced PDAC patients in combination with FOLFIRINOX (NCT05546853).