Pancreatic cancer is highly lethal, with only about 13% of patients surviving five years after diagnosis, according to the American Cancer Society. New treatments, including the NP137 antibody developed by French researchers and used alongside other drugs, may help improve outcomes.
NP137 works as an add-on therapy by blocking a key mechanism cancer cells use to resist treatment, according to lead researcher Patrick Mehlen of CNRS, the Léon Bérard Center, and Claude Bernard Lyon 1 University. The findings were published in Nature in April.
KRAS-Targeted Combination Therapy in Pancreatic Cancer
Still in clinical trials, the therapy could be paired with daraxonrasib, a promising new drug discussed at the American Society of Clinical Oncology (ASCO) meeting. Daraxonrasib targets KRAS gene mutations, which occur in around 90% of pancreatic cancer cases.
KRAS (Kirsten Rat Sarcoma) is named after early studies of cancer-causing viruses in mice, which led to the discovery of this oncogene in the 1980s. Daraxonrasib is expected to become available as early as 2027.
In a phase 1b clinical trial led by French researchers, the antibody showed improved responses to chemotherapy and increased survival in patients with locally advanced pancreatic cancer who were not eligible for surgery.
“Our work focuses on a key cellular process in embryonic development, specifically cell movement. This mechanism, known as epithelial–mesenchymal transition (EMT), allows cells to change shape and migrate. Though complex, it is essential during development.”
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Previous studies showed this process helps tumor cells spread and form metastases. In this study, French scientists found that netrin-1 drives this mechanism, promoting cancer cell migration and treatment resistance. They then created a therapeutic antibody designed to block its activity, which was tested on 43 patients after preclinical trials.
The researchers reported no signs of toxicity. The antibody was administered alone to patients with advanced disease and few treatment options. Phase 1 trials typically involve volunteers who agree to receive experimental therapy primarily to support research progress.
The lack of toxicity was anticipated, and in some cases tumors even decreased in size. Tumor biopsies before and after treatment confirmed that the antibody disrupted cancer-related processes and improved chemotherapy effectiveness.
Netrin-1 Receptor Linked to Improved Survival and Chemo Response
Researchers also found that patients with the netrin-1 receptor had longer survival and fewer relapses following chemotherapy. The latest ASCO results suggest the antibody prolongs chemotherapy’s effectiveness. While chemotherapy and immunotherapies mainly target fast-growing cells, some cancer cells can develop reduced sensitivity to these treatments.
The number of patients eligible for surgery after treatment has also risen. Only about 6% of advanced pancreatic cancer patients become operable after chemotherapy, but this rises to 23% overall and up to 40% in patients with the netrin-1 receptor.
The next phase of research, expected to take several years, will compare standard chemotherapy with combined treatment that includes the antibody. Beyond pancreatic cancer, this approach may also be explored for other tumors, such as head and neck cancers, by pairing the antibody with immunotherapy.
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