Vincenzo Nasca – Memorial Sloan Kettering Cancer Center, United States, presented his poster at ESMO GI 2026.
CLDN18.2 and KRAS signaling shape tumor states and immune microenvironment in pancreatic cancer.
“Hello everyone, my name is Vincenzo Naska. I am an Oncology Fellow at the National Cancer Institute in Milan, and since November I have been conducting a research fellowship at Memorial Sloan Kettering Cancer Center in New York, where I am leading a research project on CLDN18-positive pancreatic ductal adenocarcinoma (PDAC).
For this project, we analyzed two independent patient cohorts. One cohort included 60 patients who underwent immunohistochemistry and next-generation sequencing (NGS), with multiple biopsy time points. The second cohort consisted of patients enrolled in clinical trials who underwent single-cell RNA sequencing and spatial RNA sequencing.
The main finding of our study is that CLDN18 expression varies according to the tissue of origin of the tumor.
Specifically, CLDN18 expression is higher in primary tumors and lung metastases compared with non-lung metastases.
We also observed increased KRAS signaling in metastatic tissue.
Importantly, our analysis identified a negative correlation between KRAS signaling activity and CLDN18 expression, suggesting that CLDN18-positive PDAC may represent an intrinsic resistance mechanism to KRAS inhibition.
We are currently conducting more in-depth genomic analyses of these tissues and plan to perform in vitro studies to evaluate potential combination therapeutic strategies.
Thank you.”
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