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Despite promising rationally designed approaches aimed at blocking the transformation of epithelial cells into cancerous phenotypes, clinical progression has remained difficult to control for unclear reasons. 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Álvarez-Buylla,  \n [eabuylla@gmail.com](eabuylla@gmail.com)  \nRECEIVED 20 March 2024  \nACCEPTED 23 May 2024  \nPUBLISHED 13 June 2024  \nCITATION  \nHernández-Magaña A, Bensussen A, Martínez-García JC and Álvarez-Buylla ER (2024), Engineering principles for rationally design therapeutic strategies against hepatocellular carcinoma.  \nFront. Mol. Biosci. 11:1404319 .  \ndoi: 10.3389/fmolb.2024.1404319  \nCOPYRIGHT  \n© 2024 Hernández-Magaña, Bensussen, Martínez-García and Álvarez-Buylla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nEngineering principles for rationally design therapeutic strategies against hepatocellular carcinoma  \nAlexis Hernández-Magaña 1, Antonio Bensussen 2,  \nJuan Carlos Martínez-García 2* and Elena R. Álvarez-Buylla 1,3*  \n1Instituto de Ecología, Universidad Nacional Autónoma de México, Ciudad de México, Mexico, 2Departamento de Control Automático, Cinvestav-IPN, Ciudad de México, Mexico, 3Centro de Ciencias de la Complejidad (C3), Universidad Nacional Autónoma de México, Ciudad de México, Mexico  \nThe search for new therapeutic strategies against cancer has favored the emergence of rationally designed treatments. These treatments have focused on attacking cell plasticity mechanisms to block the transformation of epithelial cells into cancerous cells. The aim of these approaches was to control particularly lethal cancers such as hepatocellular carcinoma. However, they have not been able to control the progression of cancer for unknown reasons. Facing this scenario, emerging areas such as systems biology propose using engineering principles to design and optimize cancer treatments. Beyond the possibilities that this approach might offer, it is necessary to know whether its implementation at a clinical level is viable or not. Therefore, in this paper, we will review the engineering principles that could be applied to rationally design strategies against hepatocellular carcinoma, and discuss whether the necessary elements exist to implement them. In particular, we will emphasize whether these engineering principles could be applied to fight hepatocellular carcinoma.  \nKEYWORDS  \nhepatocellular carcinoma, cancer, rational design, cell plasticity, medical systems biology  \nIntroduction  \nCurrently, cancer is one of the most important chronic-degenerative diseases, since it is responsible for 10 million deaths per year (Ferlay et al., 2021) . However, not all cancers affect patients in the same way; it has been reported that some neoplasms such as hepatocellular carcinoma (HCC) are particularly lethal (Rumgay et al., 2022) . Thus, it is a priority to identify the molecular mechanisms involved in the malignant transformation of somatic cells and determine the factors that increase the mortality rate of cancers like HCC. In this sense, experimental reports have shown that epithelial-to-mesenchymal transition (EMT) is crucial to regulate the development of HCC (Yuan et al., 2019) . Broadly speaking, EMT is a reversible process by which epithelial cells lose cell-cell adhesion, change their morphology, and acquire properties of mesenchymal cells such ","cbCainlglcJKCydq","https://ap.wps.com/l/cbCainlglcJKCydq","pdf",3289464,14,"English","# Introduction\n## EMT and cell plasticity as therapeutic targets\n## Engineering principles and systems biology for rational therapy design","[{\"question\":\"What therapeutic target does the review emphasize for hepatocellular carcinoma?\",\"answer\":\"It emphasizes attacking EMT-related cell plasticity mechanisms, which regulate the malignant transformation of epithelial cells. The goal is to interfere with processes critical to hepatocellular carcinoma progression.\"},{\"question\":\"Why have rationally designed EMT-targeting therapies not produced major improvements?\",\"answer\":\"The review states that notable improvements have not been achieved and attributes underperformance to an incomplete understanding of mechanisms that regulate tumor cell plasticity. Without comprehensive mechanistic insight, design strategies remain limited.\"},{\"question\":\"How does the review connect engineering principles and systems biology to therapy design?\",\"answer\":\"Systems biology is presented as a way to apply engineering principles to design and optimize cancer treatments. The review discusses whether the necessary elements exist to implement these engineering concepts at the clinical level.\"}]","Engineering principles for rationally design therapeutic strategies against hepatocellular carcinoma - review | PDF",1789990637,35]