Misconceptions Thrive in the Field of Cancer as Technological Advances Continue to Confuse Stem Cell Biology.

Despite the huge thrust on targeted therapies, cancer survival rates have not improved and both cancer incidence and fatalities continue to rise globally. There is no consensus on how cancer initiates and two contrasting views were published in 2024 regarding cancer initiation. Based on the premise that no stem cells exist in tissues like liver, lungs, and pancreas but they are still affected by cancer; it was suggested that somatic cells dedifferentiate and undergo 'paligenosis' to initiate cancer. The second view discussed that tissue-resident, very small embryonic-like stem cells (VSELs) are vulnerable to extrinsic/intrinsic insults and their dysfunctions initiate cancer. The present article examines the underlying technical reasons that have led to these conflicting views. Scientists have struggled to detect quiescent cancer stem cells (CSCs) that survive chemotherapy, and radiotherapy and escape immunotherapy, cause recurrence and eventually therapeutic resistance leading to death. Lineage tracing studies fail to detect quiescent, acyclic stem cells and instead, the role of actively dividing LGR5+ cells was highlighted for tumor initiation, growth, and metastasis. Similarly, technologies like flow cytometry, and single-cell RNAseq, widely used to comprehend cancer biology, provide insights into cell populations present in abundance. Our article reviews why VSELs/CSCs in the pancreas have remained elusive despite employing advanced technologies, and the critique can be generalized to multiple other organs. This understanding is crucial as it will help to develop better therapeutic strategies for cancer, offer early detection when cancer is a weak disease, and pave the path for prevention over treatment.