ANAKOINOSIS - Re-Establishing Apoptosis Competence via Communicative Reprogramming: A Novel Anticancer Therapy (Pathophysiology - Preclinic - Clinic)

The genetic view of tumor transformation and progression led to identifying and targeting molecular cancer hallmarks, allowing selective killing of cancer cells harboring specific oncogene mutations, dramatically increasing therapy tolerability, remission rate and duration. The justified enthusiasm, however, must face the fact that many patients undergo fatal relapses: Cancer cell repopulation and high mutation rate point to intrinsic limitations, implying that a change of paradigm is required to eradicate cancer.

It is often disregarded that the cancer cell phenotype is a recessive trait, and is environmentally determined despite oncogene mutations. When considering such issues, it becomes apparent that correcting the deranged homeostasis of tumor cells and adjacent microenvironment would be a reliable therapeutic option to achieve stable tumor regression.

Communicative reprogramming therapies are a set of biomodulatory therapies aimed at resetting cancer tissue communicative rules (from the Grecian “anakoinosis”, communication) for re-establishing apoptosis competence with regulatory active drug cocktails, such as epigenetically active agents, agonists of transcription factors, metronomic low-dose chemotherapy etc..

For this purpose, it is necessary to merge the comprehensive notions on oncogenes, tumor suppressor genes and epigenetics, with the still incomplete knowledge on homeostatic pathways encompassing tumor cells, adjacent stroma, endothelial cells, immune infiltration and extracellular matrices.

Notable clinical achievements with ‘Communicative Reprogramming’ strategies indicate that this approach complies with the expectations. Otherwise refractory metastatic cancer patients would not successfully respond to anakoinosis inducing therapies despite of quite different histology or disease stages, or mutational patterns: The tools for cancer reconditioning may thus be universal, implying a prospectively more sustainable therapeutic applicability even for economic reasons.

Details for Authors –

A strong motivation for this Research Topic – which will be strictly linked to the Second Conference on “ANAKOINOSIS - Re-establishing apoptosis competence via communicative reprogramming: A novel anticancer therapy” scheduled for April 19-20 2018 in Roma - is the necessity to create a scientific network, where diversified expertise (clinics, cell-developmental- molecular biology, pharmacology, pathology, histology, etc.) converge to explain and support the potential development of biomodulatory anticancer therapies. Separate cancer-related fields may benefit from a focused exchange of information, providing more sensible means of treating cancer clinically.

It is urgent to decipher the very complex mechanisms controlling tissue homeostasis, and this requires a concerted interdisciplinary approach. Gathering studies by scientists with different expertise may be an ideal platform for assessing the cutting edge of current knowledge on the various key issues, and starting developing a network for future development.

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. Original research papers, providing novel information useful to focus the anakoinosis principles, will be also welcome. 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.

This Research Topic might be sub-divided into narrower sub-fields so that the different experts may more easily find their own collocation. Here follows a list of possible themes, considering that this does not exclude additional issues that may be proposed by the contributors and considered pertinent by the Guest Editors:

TUMOR BIOLOGY: AN EVER-CHANGING STATE-OF- THE-ART AND THE NECESSITY OF MERGING QUITE DIFFERENT RESEARCH FIELDS
 Tumor suppressor genes and tumor phenotype
 Epigenetic control of cell and tissue fate are a continuum
 Cell-autonomous and non-autonomous defence mechanisms against oncogene mutation and phenotypic tumor transformation
 Exiting from the cell: the aberrant homeostasis of cancer microenvironment in cancer genesis, progression and spreading
 Injured tissue homeostasis is differently controlled by DNA damage response in healthy and tumor tissues: loss of apoptosis competence in cancer
 Apoptosis, caspases and regeneration in injured normal and cancer tissues: a concern in anticancer therapies
 Microenvironment vs. oncogene mutations as the driving force in tumor genesis and progression: cancer phenotype and oncogene mutations are recessive traits

BIOMODULATORY APPROACHES AND COMMUNICATIVE REPROGRAMMING IN CLINICAL ANTICANCER THERAPIES: ANAKOINOSIS
 Acute myelocytic leukemia: induction of anakoinosis
 Chronic myelocytic leukemia/Langerhans cell histiocytosis: the role of pioglitazone
 How to overcome poor risk molecular-genetic parameters in APL with anakoinosis inducing therapy (ATRA plus ATO)
 Classic targeted therapy combined with anakoinosis inducing therapy
 Metronomic chemotherapy: integrating the treatment concept
 Metformin: how should we therapeutically proceed?
 Transcriptional modulators in tumor therapy
 Epigenetically modifying drugs and anakoinosis inducing therapy
 Epigenetic and differentiation therapy
 Clinical achievements with communicative reprogramming in anticancer therapy
 How to overcome the problem with undruggable targets
 Addressing molecular-genetic tumor heterogeneity in metastatic disease
 Modulatory drug combination: clinical achievements
 Therapeutic modulation of tissue homeostasis in tumor microenvironment
 Hepatocellular carcinoma and anakoinosis inducing therapy
 PPARgamma agonists as universal effectors of cancer homeostasis normalization

ANAKOINOSIS AND CANCER CARE SUSTAINABILITY
 Drug repurposing: Concepts to integrate the idea in clinical strategies
 Ever increasing costs of targeted anticancer therapies: biomodulatory therapies as a sustainable alternative
 Development of pharmacological tools for producing efficacious and economically relevant biomodulatory drug cocktails

ANAKOINOSIS, AN UBIQUITOUS PHENOMENON OF SYSTEMS BIOLOGY
 Communication between metastatic tumor and organ systems: Example cachexia

PRECLINICAL STUDIES AND EXPERIMENTAL MODELS TO EXPLORE EFFICIENT ANAKOINOSIS DRUG
COMBINATIONS
 Modulatory drug combination: translational studies
 Targeting homeostatic systems: tumor suppressor genes and homeostatic pathways
 Developing tools to study anakoinosis principles and improve its therapeutic efficacy (3D cultures,organ-on- chip, zebrafish)
 Natural compounds as anakoinosis drugs: potentials, limits and prospective developments