Ron DePinho, Professor of Department of Cancer Biology, Division of Discovery Science at MD Anderson Cancer Center, shared a post on LinkedIn:
“A very interesting translational signal in pancreatic cancer:
A new Nature Magazine study reports that adding the anti-netrin1 antibody NP137 to mFOLFIRINOX in first-line locally advanced PDAC was well tolerated, associated with encouraging survival outcomes, and, importantly, appeared to suppress EMT, a central biological program linked to therapeutic resistance. That point is what makes these findings especially provocative to me. If chemotherapy preferentially debulks the more classical state, while KRAS inhibitors appear to be particularly active against basal-like populations, then one naturally wonders whether the next step is not simply doublet therapy, but a more rational triple strategy:
KRAS inhibition + chemotherapy + EMT blockade.
In that framework, netrin1 becomes especially interesting. As a developmental cue and regulator of EMT, it may sit at a critical junction controlling plasticity, invasion, metastasis, and resistance. The observation that outcomes were longer in neogenin-high tumors further suggests that this axis may also offer a path toward biomarker-guided patient selection.
To me, the broader message is this: effective therapy for PDAC may ultimately require not only targeting tumor growth, but also constraining the cell-state transitions that allow cancer to escape one treatment and repopulate through another lineage state.
A very thoughtful piece of work, and one that may have important implications for the next generation of PDAC trial design.”
Title: Netrin1 blockade alleviates resistance to chemotherapy in pancreatic cancer
Authors: Gael Roth, Pascal Artru, Olivier Bouche, Nicolas Williet, Julien Ghelfi, Anthony Turpin, Astrid Lievre, Jean-Frédéric Blanc, Camille Evrard, Jean-Baptiste Bachet, Pauline Parent, Marc Manceau, Matthieu Roustit, Anna Borowik, Victoire Granger, Aurélie Durand, Christelle d’Engremont, Edouard Girard, Mircea Chirica, Nicolas Braissand, Nicolas Rama, Eugénie Modolo, Hector Hernandez-Vargas, Elise Georges, Patrick Mehlen
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