A Computational Model of Tumor Growth and Anakoinosis

Abstract

Anakoinosis is a new cancer treatment paradigm that posits a key role for communicative reprogramming within tumor systems. To date no mathematical or computational models of anakoinosis have been developed. Here we outline the NEATG_A system, a first computational model of communicative reprogramming. The model recapitulates key features of real tumor systems and responses to both traditional cytotoxic treatments and biomodulatory/anakoinotic treatments. Results are presented and discussed, particularly with respect to the implications for future cancer treatment protocols.

Anakoinosis: Correcting Aberrant Homeostasis of Cancer Tissue—Going Beyond Apoptosis Induction

“…Caspase-3, via proteolytic activation of phospholipase A2, elicits prostaglandin E2-mediated pro-survival paracrine signals (116), which coordinately promote the proliferation of the cancer cells surviving the cytotoxic treatment. Dying cells thus elicit a response aiming at protecting the tumor microenvironment, projecting its regeneration: hence the term "phoenix rising" (117)(118)(119), phoenix being the mythological bird that re-grows from its own ashes. This apparently paradoxical effect is in fact an evolutionarily conserved response to tissue damage (120), allowing setting up effective strategies to homeostatically repopulate an injured tissue (121).…”

“…Thus, a mathematical description of anakoinosis at the current level of knowledge regarding biological mechanisms of action seems to be problematic. However, anakoinosis may be modeled computationally using conceptual tools such as systems state, communications protocols between components representing diverse cell types and between cells and tissues (118,119). Such a communications-derived model indicates that the celltissue communication system may act as an intrinsic non-cell autonomous anticancer mechanism.…”

“…Additionally, pro-anakoinotic therapy seems to be an option in the adjuvant therapy setting for either preventing the regrowth of disseminated tumor cells or for inhibiting the growthpromoting activities of apoptotic cells (118,163).…”

Lyapunov stability of competitive cells dynamics in tumor mechanobiology

“…At the microscale level, several works suggest the adoption of models analysing the mutual effects in terms of exchanged forces to simulate cell-cell interaction [43][44][45], while tensegritybased single-cell models have been recently used to also furnish a way for biomechanically discriminating among tumor and healthy cells on the basis of the redistribution of internal pre-stretch [17,46]. At the level of cell aggregates, statistical mechanics arguments have been used to demonstrate that cells interactions represent a functional constraint to the macroscopic tumor growth law [47] and the use of evolutionary models, in the framework of population ecology, has represented a particularly successful strategy to study the dynamics of cells' collective interactions through competitive/cooperative mechanisms, in which however the feedback from the environmental on cell behaviours seems to be still absent [48][49][50][51][52][53][54]. In the light of these considerations, the full coupling of population dynamics with the tissue biomechanical response and stress-driven factors in modelling tumor growth has been the crucial point developed in very recent works by some of the present authors [27,55].…”

Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs

“…The interconnection of signaling pathways such as Nrf2, NF-κB, and STAT3, and aberrations in their activation mechanisms, make it possible to use them as a target in cancer cells for potential chemotherapeutic and/or chemopreventive compounds. This approach fits in a new trend called anakoinosis [ 26 ], the name of which derives from the ancient Greek term for “communication.” The concept of anakoinosis is an alternative to conventional chemotherapy, which is usually based on a single target, or focused on a single area of the tumor. Unlike standard therapies, treatment protocols based on anakoinosis are less likely to lead to drug resistance.…”