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Review
. 2024 Jan 2;22(1):7.
doi: 10.1186/s12964-023-01398-5.

Interplay of oxidative stress, cellular communication and signaling pathways in cancer

Muhammad Javed Iqbal  1 , Ayesha Kabeer  1   2 , Zaighum Abbas  1 , Hamid Anees Siddiqui  1 , Daniela Calina  3 , Javad Sharifi-Rad  4 , William C Cho  5
Affiliations
Review

Interplay of oxidative stress, cellular communication and signaling pathways in cancer

Muhammad Javed Iqbal et al. Cell Commun Signal. .

Abstract

Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Elevated levels of ROS disrupt cellular homeostasis and contribute to the loss of normal cellular functions, which are associated with the initiation and progression of various types of cancer. In this review, we have focused on elucidating the downstream signaling pathways that are influenced by oxidative stress and contribute to carcinogenesis. These pathways include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, and cell type transitions. Dysregulation of these pathways can lead to uncontrolled cell growth, impaired DNA repair mechanisms, and evasion of cell death, all of which are hallmark features of cancer development. Therapeutic strategies aimed at targeting oxidative stress have emerged as a critical area of investigation for molecular biologists. The objective is to limit the response time of various types of cancer, including liver, breast, prostate, ovarian, and lung cancers. By modulating the redox balance and restoring cellular homeostasis, it may be possible to mitigate the damaging effects of oxidative stress and enhance the efficacy of cancer treatments. The development of targeted therapies and interventions that specifically address the impact of oxidative stress on cancer initiation and progression holds great promise in improving patient outcomes. These approaches may include antioxidant-based treatments, redox-modulating agents, and interventions that restore normal cellular function and signaling pathways affected by oxidative stress. In summary, understanding the role of oxidative stress in carcinogenesis and targeting this process through therapeutic interventions are of utmost importance in combating various types of cancer. Further research is needed to unravel the complex mechanisms underlying oxidative stress-related pathways and to develop effective strategies that can be translated into clinical applications for the management and treatment of cancer. Video Abstract.

Keywords: Cancer; Carcinogenesis mechanisms; Oxidative stress; Reactive oxygen species.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Production of ROS in cell. ROS is generated from different redox centers (FMN, FAD, Q0) in mitochondria
Fig. 2
Fig. 2
ROS and metastasis. ROS production stimulates the induction of PI3K/AKT/mTOR and MAPK pathways that trigger metastasis
Fig. 3
Fig. 3
KEAP1-NRF2 pathway. Under oxidative stress condition, NRF2 detached from KEAP1 translocated to nucleus and trigger antioxidant response in cells by activating cytoprotective genes
Fig. 4
Fig. 4
Regulation of ROS by tumor suppressor genes. In response to ROS, tumor suppressor genes activate the expression of antioxidant genes or prooxidative genes in cells for cell survival or apoptosis respectively, to prevent tumor growth
See this image and copyright information in PMC

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