Prediction of fluctuations in a chaotic cancer model using machine learning

Sayari, Elaheh; Silva, Sidney T. da; Iarosz, Kelly C.; Viana, Ricardo L.; Szezech, José D.; Batista, Antônio M.

doi:10.1016/j.chaos.2022.112616

Cited by 4 publications

(1 citation statement)

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“…Hallmarks and pathways possess distinct implications for tumor survival, and the selection of targets among them can potentially influence the outcomes of therapeutic interventions [11,144]. The dynamics of malignant basins of attraction and the critical genes that disrupt them to drive the tumor towards cell death are contingent upon these variables [139,145]. When contemplating the therapy itself, there arises the question of how to best administer the treatment for a specific array of targets that require inhibition.…”

Section: Discussionmentioning

confidence: 99%

A Strategy Utilizing Protein–Protein Interaction Hubs for the Treatment of Cancer Diseases

Carels,

Sgariglia,

Junior

et al. 2023

IJMS

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We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient’s overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.

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