Tumors have a lower interstitial pH compared to healthy tissues, with tumor acidity having emerged as a driver of tumor progression as it can lead to tumor immune evasion. Solute carrier family 4 member 4 (SLC4A4), which encodes a sodium bicarbonate cotransporter involved in pH regulation and homeostasis in normal tissue, was the focus of studies in pancreatic cancer resistance in in vivo preclinical models. Researchers tested the impact of Slc4a4 deletion in cancer cells on tumor growth, anticancer immunity and response to immunotherapy in murine models of pancreatic ductal adenocarcinoma (PDAC).
Immunotherapeutic targeting of stage-specific embryonic antigen-4 has been shown to inhibit pancreatic cancer growth in animal models and cancer cell lines, indicating that this approach has promise for treating pancreatic ductal adenocarcinoma and possibly other SSEA-4-positive cancers, according to new a Taiwan/U.S. collaborative study.
Pretreatment with an experimental focal adhesion kinase inhibitor has been shown to improve chemotherapeutic efficiency and reduce metastasis in preclinical mouse and patient-derived models of pancreatic ductal adenocarcinoma (PDAC), with this priming regimen soon to enter phase II trials for PDAC using a novel, clinically relevant FAK inhibitor.
Two recent studies have independently identified macropinocytosis, a nutrient procurement pathway whereby cancer cells take up extracellular fluid droplets containing proteins and other macromolecules, as a promising new therapeutic target for pancreatic ductal adenocarcinoma (PDAC).
Single-cell genomic analysis has shown that mutations in the KRAS oncogene co-opt a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells, initiating pancreatic ductal adenocarcinoma, Chinese researchers reported in the November 3, 2020, edition of Nature Cancer.
