Dataset Information

The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies.

ABSTRACT: Colorectal cancer (CRC) is one of the most frequent tumor entities worldwide with only limited therapeutic options. CRC is not only a genetic disease with several mutations in specific oncogenes and/or tumor suppressor genes such as APC, KRAS, PIC3CA, BRAF, SMAD4 or TP53 but also a multifactorial disease including environmental factors. Cancer cells communicate with their environment mostly via soluble factors such as cytokines, chemokines or growth factors to generate a favorable tumor microenvironment (TME). The TME, a heterogeneous population of differentiated and progenitor cells, plays a critical role in regulating tumor development, growth, invasion, metastasis and therapy resistance. In this context, cytokines from cancer cells and cells of the TME influence each other, eliciting an inflammatory milieu that can either enhance or suppress tumor growth and metastasis. Additionally, several lines of evidence exist that the composition of the microbiota regulates inflammatory processes, controlled by cytokine secretion, that play a role in carcinogenesis and tumor progression. In this review, we discuss the cytokine networks between cancer cells and the TME and microbiome in colorectal cancer and the related treatment strategies, with the goal to discuss cytokine-mediated strategies that could overcome the common therapeutic resistance of CRC tumors.

SUBMITTER: Braumuller H

PROVIDER: S-EPMC9818504 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies.

Braumüller Heidi H Mauerer Bernhard B Andris Johanna J Berlin Christopher C Wieder Thomas T Kesselring Rebecca R

Cells 20221229 1

Colorectal cancer (CRC) is one of the most frequent tumor entities worldwide with only limited therapeutic options. CRC is not only a genetic disease with several mutations in specific oncogenes and/or tumor suppressor genes such as APC, KRAS, PIC3CA, BRAF, SMAD4 or TP53 but also a multifactorial disease including environmental factors. Cancer cells communicate with their environment mostly via soluble factors such as cytokines, chemokines or growth factors to generate a favorable tumor microenv ...[more]

PMID: 36611932

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Project description:BackgroundResistance to therapy remains a major cause of the failure of cancer treatment. A major challenge in cancer therapy is to design treatment strategies that circumvent the higher-level homeostatic functions of the robust cellular network that occurs in resistant cells. There is a lack of understanding of mechanisms responsible for the development of cancer and the basis of therapy-resistance mechanisms. Cellular signaling networks have an underlying architecture guided by universal principles. A robust system, such as cancer, has the fundamental ability to survive toxic anticancer drug treatments or a stressful environment mainly due to its mechanisms of redundancy. Consequently, inhibition of a single component/pathway would probably not constitute a successful cancer therapy.ResultsWe developed a computational method to study the mechanisms of redundancy and to predict communications among the various pathways based on network theory, using data from gene expression profiles of hepatocellular carcinoma (HCC) of patients with poor and better prognosis cancers. Our results clearly indicate that immune system pathways tightly regulate most cancer pathways, and when those pathways are targeted by drugs, the network connectivity is dramatically changed. We examined the main HCC targeted treatments that are currently being evaluated in clinical trials. One prediction of our study is that Sorafenib combined with immune system treatments will be a more effective combination strategy than Sorafenib combined with any other targeted drugs.ConclusionsWe developed a computational framework to analyze gene expression data from HCC tumors with varying degrees of responsiveness and non-tumor samples, based on both Gene and Pathway Co-expression Networks. Our hypothesis is that redundancy is one of the major causes of drug resistance, and can be described as a function of the network structure and its properties. From this perspective, we believe that integration of the redundant variables could lead to the development of promising new methodologies to selectively identify and target the most significant resistance mechanisms of HCC. We describe three mechanisms of redundancy based on their levels of generalization and study the possible impact of those redundancy mechanisms on HCC treatments.

Dataset Information

The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies.

Publications

The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies.

Similar Datasets

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