Cancer progression as a learning process

Shomar, Aseel; Barak, Omri; Brenner, Naama

doi:10.1016/j.isci.2022.103924

Cited by 12 publications

(9 citation statements)

References 120 publications

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“…The search for novel pathways to survival is necessary because stressed cells found themselves under altered conditions of MC organisms, which were not previously met during both UC and MC life, and therefore require novel solutions. Recent studies showed that individual cells demonstrate exploratory learning for adaptation to novel conditions, which is not dependent on pre-existing pathways [ 50 ]. This learning is probably performed by epigenetic remodeling, which searches via trial and error for gene expression patterns allowing survival under novel stressful conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The metastases, when cancer cells proliferate in the novel microenvironment, seemingly contradict the TOFT. However, only a very tiny part (<0.02%) of invading cells develop macro-metastases [ 50 ], which suggests that most cancer invasions are consistent with the TOFT. The TOFT assumes that the default internal cell state in MC organisms is proliferation as in UC organisms, which is bounded only by tissue constraints [ 8 , 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

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Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Vinogradov

Anatskaya

2023

IJMS

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Using meta-analyses, we introduce a unicellular attractor (UCA) model integrating essential features of the ‘atavistic reversal’, ‘cancer attractor’, ‘somatic mutation’, ‘genome chaos’, and ‘tissue organization field’ theories. The ‘atavistic reversal’ theory is taken as a keystone. We propose a possible mechanism of this reversal, its refinement called ‘gradual atavism’, and evidence for the ‘serial atavism’ model. We showed the gradual core-to-periphery evolutionary growth of the human interactome resulting in the higher protein interaction density and global interactome centrality in the UC center. In addition, we revealed that UC genes are more actively expressed even in normal cells. The modeling of random walk along protein interaction trajectories demonstrated that random alterations in cellular networks, caused by genetic and epigenetic changes, can result in a further gradual activation of the UC center. These changes can be induced and accelerated by cellular stress that additionally activates UC genes (especially during cell proliferation), because the genes involved in cellular stress response and cell cycle are mostly of UC origin. The functional enrichment analysis showed that cancer cells demonstrate the hyperactivation of energetics and the suppression of multicellular genes involved in communication with the extracellular environment (especially immune surveillance). Collectively, these events can unleash selfish cell behavior aimed at survival at all means. All these changes are boosted by polyploidization. The UCA model may facilitate an understanding of oncogenesis and promote the development of therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Vinogradov

Anatskaya

2023

IJMS

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“…Cancer progression can be considered a learning process [ 92 ]. This learning process is very costly because a large number of cancerous cells dies during cancer development [ 93 , 94 , 95 ].…”

Section: Discussion On the Universal Model Of Cancer Transformation A...mentioning

confidence: 99%

Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue

Kasperski

2022

IJMS

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In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.

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“…The resistance to anticancer agents remains the leading cause of treatment failure for many oncological patients [ 3 , 4 , 5 ]. Thus, developing a panel of biomarkers is necessary to identify chemotherapy-resistant patients.…”

Section: Extracellular Vesicles As a Tool To Monitor Chemoresistancementioning

confidence: 99%

“…Although novel therapeutic strategies have been developed, chemotherapy remains the leading approach for tumor treatment [ 2 ]. Despite significant advances in increasing the efficacy of chemotherapeutics, chemoresistance remains one of the major obstacles in cancer treatment and represents a significant risk to the survival of patients [ 3 , 4 , 5 ]. Two main classes of chemoresistance can be distinguished: intrinsic and acquired [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles and Cell Pathways Involved in Cancer Chemoresistance

Console

Scalise

2022

Life

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Chemoresistance is a pharmacological condition that allows transformed cells to maintain their proliferative phenotype in the presence of administered anticancer drugs. Recently, extracellular vesicles, including exosomes, have been identified as additional players responsible for the chemoresistance of cancer cells. These are nanovesicles that are released by almost all cell types in both physiological and pathological conditions and contain proteins and nucleic acids as molecular cargo. Extracellular vesicles released in the bloodstream reach recipient cells and confer them novel metabolic properties. Exosomes can foster chemoresistance by promoting prosurvival and antiapoptotic pathways, affecting cancer stem cells and immunotherapies, and stimulating drug efflux. In this context, a crucial role is played by membrane transporters belonging to ABC, SLC, and P-type pump families. These proteins are fundamental in cell metabolism and drug transport in either physiological or pathological conditions. In this review, different roles of extracellular vesicles in drug resistance of cancer cells will be explored.

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Cancer progression as a learning process

Cited by 12 publications

References 120 publications

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue

Extracellular Vesicles and Cell Pathways Involved in Cancer Chemoresistance

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