The phantom command: a new reading of the cell cycle through KRAS and the loss of semantic constraint: proposed theory in dialogue with the molecular vision of Italian researcher Claudia Tonelli.
Thanks to a long interview with two experts, such as Dr. Sabrina Ulivi ( Psychologist- Psychotherapist- Specialist in Clinical Psychology- Master of II level in Psychoneuroimmunology- Master in Ericksonian Hypnosis) and Dr. Giovanni Cozzolino ( Sociologist with a focus on Social Psychology- Epigeneticist Researcher- Master in Health Education) researchers and scholars for years, as well as authors of several research volumes, and Handbook directed to Universities and Physicians, we open here the scientific section, precisely on an impostant topic: the new interpretation of cancer cell behavior starting from the disconnection between energetic input and biological meaning.
Through the analysis of the behavior of KRAS mutated, is introduced, thanks to years of research by the two Italian scholars, the concept of “phantom command.” understood as a biological impulse disengaged from the functional context.
The theory stands in continuity and comparison with the molecular view proposed by Claudia Tonelli, exploring the epigenetic, informational and semantic implications of anarchoid proliferation. This theoretical reflection is grounded in an insight dating back to 1984, formalized here for the first time as a publishable hypothesis.
Italian researcher has identified the gene that turns tumors on and figured out how to turn them off, at least in the lab. The news, published in the scientific journal Cancer Research on April 2, went around the world.
Each cell is a subject that obeys. But to whom? More importantly: to what meaning?
–In the landscape of molecular alterations underlying neoplastic transformation, KRAS represents a paradigmatic example of breaking the functional link between signal and response. From this abnormality, we propose a theory that interprets tumor proliferation as a phantom command, a biological impulse that persists in the absence of meaning, context, or need.
What is the scientific context and reference to Claudia Tonelli’s vision ?
–Claudia Tonelli, a leading researcher in the field of molecular biology and transcriptional signaling, highlighted the central role of semantic coherence in molecular circuits. In her studies on the maladaptive behavior of tumor signaling pathways, Tonelli spoke of “pathological informational autonomy,” emphasizing how the cancer cell isolates itself from dialogue with the microenvironment. The present theory stands as a continuation and extension of this view, incorporating the entropic and symbolic element within the molecular analysis. The Theory of Phantasmatic Command is defined as un informational, bioenergetic state in which a cell activates its own proliferation on the basis of a deregulated internal impulse, unconstrained by external signals, and lacking semantic correspondence with its biological context.
In this state, the cell no longer responds to a signal, but indefinitely replicates a meaningless biological instruction, analogous to a molecular self-referential loop.-
Axioms of the theory
– Semantic constraint axiom: Physiological cell proliferation requires consistency between energy signal and functional context (e.g., repair, growth, immune response).
– Axiom of mutated activation: Mutations such as those in KRAS G12D or G12C alter the above constraint, keeping the cell cycle active independent of regulatory stimuli.
– Semantic entropy axiom: Loss of biological meaning generates an increase in informational entropy, with disorganized activation of epigenetic, transcriptional, and metabolic pathways.
– Dysfunctional autonomy axiom: The cancer cell acquires a false autonomy: it becomes an agent of a phantom internal command, no longer part of a cohesive organism.
What are the Implications and Hypotheses related to said theory?
– Neoplasia vien e seen as a semiotic disconnect: The cancer cell loses the ability to interpret signals, acting on an “authorless” impulse. Some highlights:
– Self-referential epigenetic restructuring: Continued activation of mutated KRAS induces an autonomous epigenetic landscape, with selection of pro-survival pathways (e.g., MYC, mTOR, HIF1a) disconnected from the microenvironment.
– Role of NRF2: Under tumor conditions, NRF2 loses its protective function and becomes complicit in phantom command, protecting cells that should no longer replicate.
The vision proposed by the two researchers Ulivi and Cozzolino, while starting from a precise molecular datum (KRAS), opens a dialogue with broader dimensions: the ontology of biological command, the semantic function of intracellular signals, and the possibility that the cancer cell is the first “disconnected subject” of post-genomic biology.
In this sense, the theory of phantasmal command is not only a molecular description, but an epistemological hypothesis on the loss of meaning in complex living systems.
Conclusions and prospects?
“Once, in 1984, I imagined that the cell could go mad as a speechless body. Today, thanks in part to those like Claudia Tonelli who courageously bring forward the science of our time, I can attempt to formulate that vision in a language that can be shared.”
The Theory of Phantom Command opens once again, and more, today new spaces for the interpretation of oncogenesis and suggests new avenues for therapeutic approaches as well: perhaps, in the future, it will not be enough to deactivate the signal, but meaning must be restored.
Bibliography
- Cox, A. D., et al. (2014). Drugging the undruggable RAS: Mission possible? Nature Reviews Drug Discovery, 13(11), 828-851.
- Prior, I. A., et al. (2020). The frequency of Ras mutations in cancer. Cancer Research, 80(14), 2969-2974.
- Hayes, J. D., et al. (2020). Oxidative stress in cancer. Cancer Cell, 38(2), 167-197.
- Zhang, D. D. (2006). Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metabolism Reviews, 38(4), 769-789.
- Romero, R., et al. (2017). Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nature Medicine, 23(11), 1362-1368.
- Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646-674.
- Esteller, M. (2008). Epigenetics in cancer. New England Journal of Medicine, 358(11), 1148-1159.
- Barabási, A. L., et al. (2011). Network medicine: a network-based approach to human disease. Nature Reviews Genetics, 12(1), 56-68.
- Tonelli, C., et al. (2018). Transcriptional regulation by Nrf2. Antioxidants & Redox Signaling, 29(17), 1727-1745.
- Kinzler, K. W., & Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell, 87(2), 159-170.
