Stem Cell Theory of Cancer: Rude Awakening or Bad Dream from Cancer Dormancy?

Abstract

To be dormant or not depends on the origin and nature of both the cell and its niche. Similar to other cancer hallmarks, dormancy is ingrained with stemness, and stemness is embedded within dormancy. After all, cancer dormancy is dependent on multiple factors such as cell cycle arrest, metabolic inactivity, and the microenvironment. It is the net results and sum effects of a myriad of cellular interactions, interconnections, and interplays. When we unite all cancer networks and integrate all cancer hallmarks, we practice and preach a unified theory of cancer. From this perspective, we review cancer dormancy in the context of a stem cell theory of cancer. We revisit the seed and soil hypothesis of cancer. We reexamine its implications in both primary tumors and metastatic lesions. We reassess its roles in cell cycle arrest, metabolic inactivity, and stemness property. Cancer dormancy is particularly revealing when it informs us about the mysteries of late relapse, prolonged remission, and second malignancy. It is paradoxically rewarding when it delivers us the promises and power of cancer prevention and maintenance therapy in patient care.

Very Late Recurrence in Germ Cell Tumor of the Testis: Lessons and Implications

“…The mechanisms that activate tumor cells from dormancy into a proliferative state remain unknown. It is conceivable that genetic mutations may occur and accumulate in the micrometastatic cells that could trigger activation from dormancy and the resultant LR, or perhaps activation from dormancy involves a change in the microenvironment of the tumor cells [ 27 , 28 ]. Further research is needed to investigate the biology of LR.…”

Unveiling the role of cellular dormancy in cancer progression and recurrence

“…The pervasiveness of dormancy may come from its connections to many established hallmarks of cancer – such as resistance to cell death, genomic mutations, deregulation of metabolism and metastases [28,29 ▪ ]. Similarly, the transient nature of dormancy, wherein cells eventually resume active proliferation, reflects cancer's inherent ability to evade growth suppression mechanisms and sustain proliferative signaling – further reinforcing the association between dormancy and cancer hallmarks [30].…”

Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions

“…Indeed, several markers expressed in CSCs can also be found in adult tissue-resident stem cell populations [ 79 ]. In order to describe this particular type of cell, we kept the term of CSCs, knowing that it could be the subject of controversial theories [ 80 , 81 ]. CSCs are defined as dedifferentiated cells that have unlimited proliferation and self-renewal abilities and can reinitiate and reconstitute tumor heterogeneity [ 82 ].…”