The Molecular Connections between Lung and Pancreatic Cancer Metastases: are we not seeing the Forest for the Trees?

Abstract

Metastases to the pancreas are rare at 1-2%. Among primaries metastasizing to the pancreas, lung cancer (LC) is frequently the culprit. Metastases to the lung from pancreatic cancer (PC) are significantly more common at about 45%, presenting striking differences in cancer behavior. There are conflicting reports regarding cancerogenicity and metastatic incidence between the lung and pancreas. Therefore, this review takes a fresh look at lung and pancreatic cancer behavior. Secondary metastases to the lung and pancreas are often indistinguishable from LC and PC primaries, and the seed and soil hypothesis is not always congruous with clinical interpretation of disease course. Sometimes single "seed" dissemination is thought to occur at the preneoplastic stage without any evidence of tumor invasion. Metastatic growth may become dormant, manifesting years later as cancer of unknown primary (CUP). Interestingly, CUPs are discovered to originate most frequently from LC and PC primaries at autopsy. The lung and pancreas are morphologically related through endoderm-level morphogenesis. The molecular basis of cancer regularity between them involves developmental signaling pathways including HEDGEHOG, NOTCH, WNT, and CXCL12/CXCR4, an evolving genetic background, and regulatory tumor-stromal interactions. Perhaps biomarkers that explain the regularity between them have been documented -as we peruse the bioscience literature for information, we may be reading through viable biomarkers and solutions and not seeing the forest for the trees. On the other hand, perhaps more research is warranted to explain cancer behavior between the lung and pancreas. Observations in this review provide a framework on which to extract clues for future work regarding organspecific metastasis between the lung and pancreas.