Pancreatic cancer: an antibody proves itself in an early clinical trial
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Pancreatic cancer, which affects a growing number of patients, remains one of the most aggressive forms due to the ability of cancer cells to resist traditional treatments such as chemotherapy. With this in mind, a team led by scientists from the CNRS1 , the Léon Bérard Centre, the Inserm and l’Université Claude Bernard Lyon 1 has developed an antibody that can block one of the resistance mechanisms of cancer cells. Assessed by the researchers during a phase 1b clinical trial coordinated by the medical team in digestive oncology from l’Université Grenoble Alpes and Grenoble Alpes CHU – with financial support from the Fondation ARC and the start-up NETRIS Pharma2 – the antibody improved chemotherapy response and survival rate for patients with locally advanced and initially inoperable pancreatic cancer. The results will be published on 22 April in Nature.
In many cancers, some tumour cells resist treatment by activating what is referred to as “epithelial-to-mesenchymal transition,” by which they quickly change shape and behaviour, thereby avoiding standard treatments. A team supervised by scientists from the Cancer Research Centre of Lyon (Centre de lutte contre le cancer Léon Bérard / CNRS / Inserm / Université Lyon 1) has shown that this mechanism is partially based on the abnormal activation, during tumour progression, of a protein ordinarily present only during embryonic development: netrin-13 .
Armed with this discovery, the scientists developed an antibody, NP137, that can attach to netrin-1 and prevent the protein from interacting with its cellular receptor, thereby blocking the epithelial-to-mesenchymal transition of tumour cells4 . The tumours subsequently become more sensitive to anticancer treatment.
After promising initial data among animals and humans4 , this drug candidate recently proved itself in a phase 1b clinical trial (LAPNET-1)5 among 43 patients with locally advanced and initially inoperable pancreatic cancer. Administered in association with standard chemotherapy, NP137 can significantly improve the duration of chemotherapy response, and even extend overall patient survival compared to historical data for patients treated exclusively with standard chemotherapy. This effect is especially visible for patients whose tumours have the netrin-1 receptor, for whom the treatment extended progression-free post-chemotherapy survival by an average of more than 5 months6 .
While these results must be confirmed by a clinical trial of broader scope7 , they offer a promising therapeutic option for this steadily rising cancer, which will become the second cancer-related cause of death by the 2030s. This therapeutic avenue could eventually be extended beyond pancreatic cancer, with potential applications in many other types of tumours possessing the same resistance mechanism.
- 3https://doi.org/10.1038/nrc3005
- 4 a b
- 5Conducted by the Grenoble Alpes CHU and coordinated by Gaël Roth, a Professor and Hospital Practitioner at l’université Grenoble Alpes and the Grenoble Alpes CHU, as well as a specialist on hepatobiliary and pancreatic cancers.
- 6In this study among patients showing the presence of the netrin-1 receptor, progression-free survival is on average 15.65 months, with the average global survival rate still undetermined at the time of analysis. When only standard chemotherapy is used, progression-free survival is 6-10 months, and overall survival 11-15.
- 7The launch is planned to take place by the end of 2026.
Netrin1 blockade alleviates resistance to chemotherapy in pancreatic cancer. Gael Roth et al. Nature, le 22 avril 2026.
