Birth of a solid organ cancer—the cell fusion hypothesis presented with pancreatic cancer as a model: A narrative review

Objective: This hypothesis-driven narrative review aims to explore the evidence for the fundamental process of cell fusion between normal, but different, cell types in the genesis of a cancer cell. Background: Finding out how a cancer is born must remain a top priority as this will allow us the opportunity to understand the disease before it acquires its largely ‘untameable’ heterogeneous form. The search for the cell of origin in solid organ cancers has remained elusive despite concerted attempts over many decades. There is always more than one cell type implicated in the causation of solid organ cancers. Methods: Based on preliminary data from our laboratory and a review of the evidence in literature, we present a novel hypothesis to explain the origin of solid organ cancers using pancreatic cancer as an example. Conclusions: We hypothesize that, “Cancer is born from fusion and hybridization of normal cells from two different lineages located within the vicinity of each other that perceive a signal reminiscent of a threat to their extinction that leads to epigenetically-mediated transformations permitting them to achieve cell fusion.” Addressing this hypothesis to prove, or disprove it, presents an opportunity to unravel the basis of carcinogenesis and potential re-think our strategies for treatment in terms of choice of chemotherapeutic agents, dosage of chemo- and radiation-therapy, and timing of interventions (surgery, chemotherapy and radiation therapy).