Understanding Cancer as a Systemic Disease by Understanding Neural Stemness as the Core Property of Cancer Cell

Cancer is a systemic disease with multilayered complexity. Some theories/hypotheses have been proposed to explain cancer. They are successful in explaining certain aspects of cancer, but meet serious challenges in other aspects. Inappropriate understanding of cancer cell and cancer also hinders the development of more effective strategies of cancer therapy. My previous studies demonstrated that the core property of cancer (tumorigenic) cells is neural stemness. The finding led to the subsequent discovery about the central role of neural stemness during tumorigenesis and a novel paradigm that can hopefully explain systemic complexity of cancer as a whole. In the review, I summarize the evidence from evolutionary, developmental biology and cancer biology research supporting that neural stemness, referring to the collective property of embryonic neural/neural stem cells, represents the general stemness, the cellular property that determines both pluripotency and tumorigenicity. I make detailed discussion about the key role of neural stemness in understanding the core property and phenotypic traits of cancer cell and in understanding cancer complexity. These pieces of evidence and discussion reveal that cancer is the manifestation of the power of general rules dictating both embryogenesis and tumorigenesis. Briefly, acquiring neural stemness in ectodermal cells during embryogenesis, i.e., neural induction, leads to body axis formation, and ectopic neural induction causes a conjoined twin in an embryo; whereas acquirement of neural stemness in cells of a postnatal animal/human results in a degenerated conjoined twin-like structure, i.e., a tumor. Due to the causal role of neural stemness in tumorigenesis, novel strategies of cancer therapy can be developed by targeting neural stemness using the principle of pluripotent cell differentiation. In addition, some essential issues worth considering in cancer research are also discussed.