Intracellular and intercellular signaling networks in cancer initiation, development and precision anti-cancer therapy

Abstract

Cancer initiation and development are increasingly perceived as systems-level phenomena, where intra- and inter-cellular signaling networks of the ecosystem of cancer and stromal cells offer efficient methodologies for outcome prediction and intervention design. Within this framework, RAS emerges as a ‘contextual signaling hub’, i.e. the final result of RAS activation or inhibition is determined by the signaling network context. Current therapies often ‘train’ cancer cells shifting them to a novel attractor, which has increased metastatic potential and drug resistance. The few therapy-surviving cancer cells are surrounded by massive cell death triggering a primordial adaptive and reparative general wound healing response. Overall, dynamic analysis of patient- and disease-stage specific intracellular and intercellular signaling networks may open new areas of anticancer therapy using multitarget drugs, drugs combinations, edgetic drugs, as well as help design ‘gentler’, differentiation and maintenance therapies.

The Complexity of the Homeopathic Healing Response Part 1: The Role of the Body as a Complex Adaptive System in Simillimum-Initiated Recovery from Disease

“…The implication is that advanced treatment strategies, such as homeopathic simillimum medicine dosing, will also modulate the inter-relationships and interactions of endogenous biological signaling networks and gene expression, a hypothesis supported by studies of certain homeopathic medicines in animal or cellular models for cancer. 44,51,[77][78][79] If the system is already diseased in some way, it is at or close to its physiological limits (cf., TDS and oscillation). 61,62,80,81 The body will potentially exhibit transient aggravation up to its physiological limits and then reverse its direction of change back from disease toward a healthier degree of complexity, following the arrival of a low-dose, hormetic salient stimulus to do so.…”

“…41 In developing diseases such as cancer, the process engages the complex signaling networks or inter-connected intracellular and extracellular pathways of the body as a complex adaptive system/network. 28,34,[42][43][44] In disease, the body is an open, self-organized complex adaptive system that is out of equilibrium as a consequence of its responses to environmental stressors. Consequently, the body generates patterns of symptoms that are emergent, indirect results of the overall disease process.…”

The Complexity of the Homeopathic Healing Response Part 2: The Role of the Homeopathic Simillimum as a Complex System in Initiating Recovery from Disease

“…The implication is that using the homeopathic simillimum medicine as a personalized hormetin will modulate the interrelationships and interactions of endogenous biological signaling networks to initiate disease recovery, a hypothesis supported by studies of certain homeopathic medicines in animal or cellular models for cancer. [189][190][191][192][193] If the system is already diseased in some way, it is at or close to its physiological limits (cf. time-dependent sensitization and oscillation).…”

Addressing cancer signal transduction pathways with antisense and siRNA oligonucleotides

“…Tumors can also influence their local and distant microenvironments through signaling processes that affect angiogenesis, inflammation and modulation of potential metastatic sites ( 4 , 5 ). In considering therapeutic intervention in cancer signal transduction, it is important to recall that these pathways are highly convoluted, with multiple interconnections between pathways as well as numerous feedback and feed-forward control mechanisms ( 6 ). Thus, perturbation of one pathway can have unintended consequences for other pathways; this reality has often impeded the development of therapies directed toward signaling.…”