Unraveling the molecular mechanisms of tumor metastasis: Insights and therapeutic strategies

This review is initiated by Prof. Wenwen Xu, Prof. Bin Li, and Prof. Xingyuan Shi, and focuses on the molecular mechanisms underlying tumor metastasis, which is the primary cause of cancer-related deaths and a major clinical challenge. Tumor metastasis is a multi-step process that includes the detachment of tumor cells from the primary site, invasion into the blood and lymphatic systems, colonization of distant organs, and angiogenesis. Despite recent advancements in understanding the signaling pathways involved in metastasis, tumor microenvironment (TME) interactions, and epigenetic regulation, the precise molecular networks driving metastasis remain largely unresolved. Moreover, there is a lack of clinically translatable targeted therapies for metastasis. Therefore, a deeper understanding of the dynamic regulatory mechanisms involved in metastasis is crucial for identifying new therapeutic targets and developing precise intervention strategies. These insights not only promise to improve our understanding of metastatic progression but also hold the potential for the development of novel therapeutic approaches that may reduce the incidence of metastasis and improve patient outcomes.

This review provides an in-depth analysis of the genetic, epigenetic, and molecular mechanisms that contribute to the metastatic process. The authors delve into the roles of genetic mutations, chromosomal instability (CIN), and epigenetic modifications in promoting metastasis. CIN, as an essential driver of metastasis, contributes to genomic instability and clonal selection, which enhances the tumor’s adaptability and invasiveness. In addition, epigenetic alterations, such as chromatin remodeling, DNA methylation, RNA modifications, and non-coding RNA regulation, control gene expression without altering the DNA sequence, and contribute to the pro-metastatic phenotype. These epigenetic mechanisms also play pivotal roles in drug resistance and immune evasion, both of which are critical challenges in cancer treatment.

A key focus of the review is the tumor microenvironment, which plays a central role in cancer progression, metastasis, and resistance to therapy. The tumor microenvironment is composed of multiple components, and its characteristics such as hypoxia, acidity, chronic inflammation, and immunosuppression promote tumor metastasis. The cellular components in the tumor microenvironment, such as cancer stem cells, stromal cells, and immune cells, interact with tumor cells, influencing the development and metastasis of tumors. In addition, the tumor microenvironment is highly heterogeneous. There are differences in the tumor microenvironment among different cancer types and even in different metastatic sites of the same cancer, which affects the metastatic pattern and treatment response.

The review also discusses the impact of specific genetic mutations and epigenetic alterations in the context of metastasis. For example, chromosomal instability and mutations in key tumor suppressor genes and oncogenes contribute to the acquisition of invasive properties by tumor cells. Additionally, the authors highlight the role of RNA modifications in regulating metastasis, providing insight into how these post-transcriptional modifications contribute to the metastatic phenotype. Moreover, the TME influences the epigenetic landscape of tumor cells, which further drives metastatic behavior. The interaction between tumor cells and their surrounding microenvironment is crucial in determining the fate of metastatic cells and their ability to colonize distant tissues.

In conclusion, the review provides valuable insights into the complex interplay between genetic, epigenetic, and environmental factors that drive tumor metastasis. The development of personalized medicine and clinical oncology has deepened our understanding of tumor metastasis. However, there are still many challenges, such as the incomplete understanding of metastatic mechanisms, the lack of precise experimental models, the high cost of drug development, tumor heterogeneity, and drug resistance. In the future, it is necessary to further study the metastatic mechanisms, develop more accurate experimental models, explore new therapeutic targets and drugs, integrate multi-omics data, and leverage artificial intelligence technology to promote the development of tumor metastasis treatment and improve patient prognosis.

See the article:

Tumor Metastasis: Mechanistic Insights and Therapeutic Intervention

https://doi.org/10.1002/mog2.70012