Adenosquamous cancer of the pancreas: decoding the epitome of tumor cell plasticity and defining unique therapeutic angles

Pancreatic cancer is an increasingly common malignancy with delayed diagnoses and generally
ineffective treatments. Among these, pancreatic ductal adenocarcinoma (PDAC) is most common,
accounting for 90% of cases. However, this proposal focuses on Adenosquamous Cancer of the
Pancreas (ASCP), a particularly rare and deadly form representing less than 5% of pancreatic
cancers, and currently lacking specific treatment protocols. ASCP exemplifies extreme tumor cell
plasticity, presenting both an adenocarcinoma and a squamous component within the same patient—
a phenomenon not well-understood.
The applicants, known for their significant past contributions to PDAC research, aim to employ
advanced single cell resolution (spatial) transcriptomic profiling techniques and experimental models
to elucidate and manipulate key regulators of cell plasticity. This research will also refine and test
novel treatment approaches by integrating existing knowledge and new data generated in this
project.
This collaborative effort involves meticulous sample collection from ASCP tumors, and combines
unique computational and cell biology expertise from both partners. Beyond investigating ASCP, the
project seeks to advance our understanding of pancreatic tumor cell plasticity in general, potentially
paving the way for targeted therapies. The project emphasizes knowledge transfer and expansion
with wide applications.