Melvin Sanicas, Physician-Scientist MBA, Global Medical Strategy Leader at Bavarian Nordic shared a post on LinkedIn:
“New research from Duke-NUS Medical School uncovers a molecular “switch” that may help make one of the deadliest cancers more treatable.
In a study published in the Journal of Clinical Investigation, researchers led by Prof David Virshup found that pancreatic cancer cells can shift between two states: a more organized, treatment-responsive ‘classical’ subtype and a more aggressive, chemotherapy-resistant ‘basal’ subtype.
The team discovered that this transition is controlled by the gene GATA6. When GATA6 levels are high, tumors tend to be more structured and respond better to chemotherapy. When GATA6 is suppressed – through signaling from the KRAS-ERK pathway – cells become more aggressive and resistant to treatment.
The researchers showed that blocking this KRAS-ERK signaling pathway can restore GATA6 activity and push cancer cells back toward a more treatment-sensitive state. Combining targeted inhibitors with standard chemotherapy produced stronger effects than either treatment alone.
According to Prof SheeMei Lok, these findings help explain why pancreatic tumors often resist chemotherapy and point to a rational strategy for combining targeted therapies with existing drugs. Prof Patrick Tan, MD-PhD added that understanding how cancer cells switch states could guide more strategic treatment design – not just for pancreatic cancer, but for other cancers driven by KRAS mutations.
This work highlights how insights from basic cancer biology can reveal new therapeutic opportunities for one of the most difficult cancers to treat.
Zheng Zhong et al, Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer, Journal of Clinical Investigation (2025).”
Title: Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer
Authors: Zheng Zhong, Xinang Cao, Pei-Ju Liao, Raman Sethi, Jeffrey A. Klomp, Clint A. Stalnecker, Jinmiao Chen, Yue Wan, Channing J. Der, David M. Virshup
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