Anticancer therapies are aimed at killing cancer cells to reduce tumor mass. Unfortunately, repopulation too often ensues, causing fatal relapses. This intrinsic limit calls for a change of paradigm: could cancer tissues, instead of cancer cells, be targeted by therapeutic strategies aiming at tissue “re-education”?

Anakoinosis (from the ancient Greek for communication), is a paradigmatic new therapy aimed at correcting aberrant cancer homeostasis by re-activating lost tissue defenses. Originally designed for palliative care, using combinations of compounds acting as “master modulators” of gene expression and tissue communication signals, avoiding cytotoxic drugs, anakoinosis has shown unexpected long-lasting anticancer potential in the clinical context, reaching even continuous complete remission of otherwise untreatable metastatic cancers. Mechanistically, in anakoinosis “re-formatted” cancer tissues, tumor cells are not necessarily killed, but can remain and re-acquire ‘normal’ functions, for example by differentiation or transdifferentiation, even when displaying abnormal oncogenic patterns.

Such achievements transcend the classical genetic view of cancer biology, and need to be framed in a modern and solid scientific context. Notably, basic researchers and oncologists increasingly report experimental and clinical observations which imply that tissues and organisms obey laws that go beyond the strict gene- or cell-autonomous regulatory circuitry in tumor biology. A strong motivation for this Research Topic is therefore to begin building a repository where such ever-increasing scattered observations may be shared, compared and contextualized. This will pave the way for a coherent structural framework to develop knowledge on Molecular Tissue Dynamics in the context of cancer microenvironment.

This will open a prospect for conceptually new biomodulatory compounds acting to correct molecular tissue dynamics, implying sustainable drug development in anticancer therapies. In this view, we solicit the participation of Researchers active in the area of clinical oncology, translational studies, basic cell/tissue biology research, regenerative medicine, theoretical modelling, systems biology, innovative technological tools, pharmacology and drug design. Topics include interdisciplinary approaches to anakoinosis such as:

• Anakoinosis clinical strategies: Biomodulation and communicative reprogramming in anticancer therapies; correcting dysregulated cancer homeostasis for long-term tumor control; remodeling cancer phenotype beyond apoptosis induction; systemic signatures of cancer as therapeutic guidance
• Anakoinosis clinical tools: targeted therapy combined with anakoinosis; metronomic chemotherapy; transcriptional modulators and epigenetically modifying drugs; master modulators (e.g., metformin, PPARγ agonists, retinoic acid)
• Biological bases of anakoinosis: molecular tissue dynamics: apoptosis and compensatory proliferation; DNA damage response as homeostatic supervisor; epithelial control of oncogene functions; complex regulatory levels (e.g., super-enhancers, scaffold proteins, interfering RNAs); homeostatic pathways; stress response, autophagy, redox and metabolic pathways; homeostatic role of immune regulatory circuitries.
• Novel technical approaches to study anakoinosis: new prospects in animal models; high tech in vitro studies; projecting in vitro the cancer microenvironment; mathematical modelling of cancer dynamics
• Anakoinosis, a novel opportunity for sustainable drug development: immunotherapy; new bio-modulatory drugs and combinations; bioinformatic approaches; nanomedicine; drug repurposing

The Research Topic is open, though not exclusively, to the speakers of the Third International Conference on Anakoinosis (Rome, Italy, May 13th-15th). We expect that the contributors provide general Review papers in their own specific fields, focusing on the connections that link their area of expertise with the backbone of the Research Topic. We likewise welcome Original Research Papers, providing novel information useful to focus the anakoinosis principles. Given the high interdisciplinary nature of this Research Topic, which is ideally destined to a very broad readership, we will ask contributors to pay particular care to making the introduction section of their studies (either experimental or review), especially clear and comprehensible to non-specialists, in order to facilitate the exchange of knowledge.

The Topic Editors would like to acknowledge the contribution of Francesca Corsi in the co-ordination of this Research Topic.

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