Anastasis and Other Apoptosis-Related Prosurvival Pathways Call for a Paradigm Shift in Oncology: Significance of Deintensification in Treating Solid Tumors
Bibliographic record
Abstract
What is apoptosis? The Nomenclature Committee on Cell Death and numerous other pioneering cancer/p53 biologists use the terms "apoptosis" and "cell death" interchangeably, disregard the mind-numbing complexity and heterogeneity that exists within a tumor (intratumor heterogeneity), disregard the contribution of polyploid giant cancer cells (PGCCs; the root causes of therapy resistance and relapse) to this heterogeneity, and then propose novel apoptosis-stimulating anticancer strategies. This is shocking for the following three reasons. First, clinical studies reported since the 1990s have revealed that increased apoptosis in solid tumors is associated with increased tumor diversity and poor prognosis. Second, we have known for years that dying (apoptotic) cancer cells release a panel of secretions (e.g., via phoenix rising and other pathways) that promote metastatic outgrowth. Third, over a decade ago, it was demonstrated that cancer cells can recover from late stages of apoptosis (after the formation of apoptotic bodies) via the homeostatic process of anastasis, resulting in the emergence of aggressive variants. The cell surface expression of CD24 has recently been reported to be preferentially enriched in recovered (anastatic) cancer cells that exhibit tumorigenic properties. These and related discoveries outlined herein call for a paradigm shift in oncology to focus on strategies that minimize the occurrence of treacherous apoptosis and other tumor-repopulating events (e.g., therapy-induced cancer cell dormancy and reactivation). They also raise an intriguing question: is deregulated anastasis (rather than evasion of apoptosis) a hallmark of cancer?
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.002 | 0.005 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.007 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".