Stem Cell Origin of Cancer: Implications of Oncogenesis Recapitulating Embryogenesis in Cancer Care

Abstract

From this perspective, we wonder about the clinical implications of oncology recapturing ontogeny in the contexts of neoantigens, tumor biomarkers, and cancer targets. We ponder about the biological ramifications of finding remnants of mini-organs and residuals of tiny embryos in some tumors. We reminisce about classical experiments showing that the embryonic microenvironment possesses antitumorigenic properties. Ironically, a stem-ness niche—in the wrong place at the wrong time—is also an onco-niche. We marvel at the paradox of TGF-beta both as a tumor suppressor and a tumor promoter. We query about the dualism of EMT as a stem-ness trait engaged in both normal development and abnormal disease states, including various cancers. It is uncanny that during fetal development, proto-oncogenes wax, while tumor-suppressor genes wane. Similarly, during cancer development, proto-oncogenes awaken, while tumor-suppressor genes slumber. Importantly, targeting stem-like pathways has therapeutic implications because stem-ness may be the true driver, if not engine, of the malignant process. Furthermore, anti-stem-like activity elicits anti-cancer effects for a variety of cancers because stem-ness features may be a universal property of cancer. When a fetus survives and thrives despite immune surveillance and all the restraints of nature and the constraints of its niche, it is a perfect baby. Similarly, when a neoplasm survives and thrives in an otherwise healthy and immune-competent host, is it a perfect tumor? Therefore, a pertinent narrative of cancer depends on a proper perspective of cancer. If malignant cells are derived from stem cells, and both cells are intrinsically RB1 negative and TP53 null, do the absence of RB1 and loss of TP53 really matter in this whole narrative and an entirely different perspective of cancer?

The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance

“…Cancer stem cells seem to play an essential role in chemoresistant tumor relapse [ 109 , 110 ]. It was proposed that stemness represents a driver for tumor and cancer relapse [ 111 , 112 ]. On the other hand, Trop-2 expression has been found to be associated with stem cells in prostate cancer [ 16 , 25 , 113 ].…”

Stem Cell Theory of Cancer: Clinical Implications of Epigenomic versus Genomic Biomarkers in Cancer Care

“…Therefore, we predict that the conception and application of treatments which control or eliminate CSCs could provide substantive rather than nominal clinical benefits in cancer care [100][101][102][103]. How to complement novel CSC-targeted therapy with conventional non-CSC-targeted therapy is key in therapy versus drug development, to provide breakthrough rather than marginal improvements, and exponential rather than incremental improvements in clinical outcomes [11,104].…”

Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care

“…Tyrosine kinase inhibitors (TKI) are known to be teratogenic because they disrupt embryogenesis; however, they also interfere with oncogenesis and are therapeutic in cancer care [ 147 ].…”