Unravelling the therapeutic potential of dual TGFβ-1 and CXCR4 inhibition in breast cancer using computational strategies

Abstract

Background and rationale The incidence and mortality of breast cancer (BC) continue to increase, making it a matter of public health concern worldwide. Despite the various strides made in breast cancer (BC) research, the molecular mechanisms driving its progression remain incompletely understood, particularly the role of key regulatory genes in tumor development and therapy resistance. TGFβ-1, IL19, CXCR4, BMP1, VCAN, and WNT2 have been implicated to be instrumental to critical oncogenic pathways; however, their cumulative contribution toward the pathophysiology of BC has not yet been investigated. Therefore, the present study utilizes an integrative bioinformatics approach to decipher their functional relevance, providing a basis for targeted therapies. Methods and analytical approach TGF-β1, IL19, CXCR4, BMP1, VCAN, and WNT2 are among the important genes in BC that we have studied in great detail using bioinformatics techniques that detail differential gene expression analysis for their dysregulation in BC. Their broader oncogenic implications were then clarified by performing pan-cancer and pathway enrichment analyses. Molecular docking studies were employed to comprehend the functional interactions and potential therapeutic targets in protein-protein interaction (PPI) networks. Key findings It is demonstrated by our study that TGFβ-1 and CXCR4 are critical factors in the tumorigenesis of BC and their inhibition shows interference with tumor-associated pathways in a synergistic way. Computational modelling suggests that concomitant inhibition of these two targets, with D4476 and AMD3100, may show therapeutic value through modulation of certain key signalling cascades. Conclusion and significance This study provide new insights into the molecular basis of BC and support the idea of targeting TGFβ-1 and CXCR4 together for therapy. The above findings lay the foundation for future in vitro and in vivo experiments aimed at demonstrating that inhibition of both factors would be a viable strategy to improve the therapeutic outcome in BC.