Affecting a growing number of patients, pancreatic cancer remains one of the most aggressive due to the ability of cancer cells to resist conventional treatments such as chemotherapy. A team led by scientists from CNRS, Centre Léon Bérard, Inserm, and Université Claude Bernard Lyon 1 has developed an antibody capable of blocking one of the resistance mechanisms of cancer cells.
Evaluated by scientists in a phase 1b clinical trial coordinated by the medical team of digestive oncology at Université Grenoble Alpes and CHU Grenoble Alpes, with financial support from the ARC Foundation and the startup NETRIS Pharma, this antibody improved the response to chemotherapy and increased survival in patients with locally advanced pancreatic cancer that was initially inoperable. The results were published on April 22 in
Nature.
3D illustration of the pancreas
© Fotalia In many cancers, some tumor cells resist treatments by activating a mechanism known as "epithelial-mesenchymal transition," through which they rapidly change their shape and behavior, thereby acquiring the ability to evade standard treatments.
A team supervised by scientists from the Cancer Research Center of Lyon (Léon Bérard Cancer Center / CNRS / Inserm / Université Lyon 1) has shown that this mechanism partly relies on the abnormal activation, during tumor progression, of a protein that is normally present only during embryonic development: netrin-1.
Based on this discovery, the scientists developed an antibody, NP137, capable of binding to netrin-1 and preventing the protein from interacting with its cellular receptor, thus blocking the epithelial-mesenchymal transition of tumor cells. Result: tumors become more sensitive to anticancer treatments.
After promising initial data in animals and humans, this candidate drug has now proven itself in a phase 1b clinical trial (LAPNET-1) involving 43 patients with locally advanced pancreatic cancer that was initially inoperable.
Administered in combination with standard chemotherapy, NP137 significantly improved the duration of response to chemotherapy and even prolonged overall survival compared to historical data from patients treated with standard chemotherapy alone. This effect is particularly visible in patients whose tumors carry the netrin-1 receptor, for whom the treatment was associated with an average prolongation of more than 5 months in progression-free survival after chemotherapy.
While these results need to be confirmed by a larger clinical trial, they open a promising therapeutic option for this fast-growing cancer, which is expected to become the second leading cause of cancer death by 2030-2040. In the long term, this therapeutic approach could go beyond pancreatic cancer, with possible applications in many other tumor types that share the same resistance mechanism.