Navigating chemoresistance in triple-negative breast cancer: interplay between molecular signalling pathways and immune microenvironment.

Triple-negative breast cancer (TNBC) therapeutic strategies remain a challenge as the mechanisms in the development of chemoresistance remains elusive. Previous evidence has shown enhancement of the immunomodulatory clusters of genes and immune regulators in TNBC such as the tumor infiltrating leukocyte (TILs – PD-L1, CTLA4, CD8 etc.) playing critical roles in cancer progression and chemoresistance in some cancers. TNBC chemoresistance undergoes multiple hallmarks of cancer, including genomic instability driven by TP53 gain-of-function and BRCAness thus resulting to immune pressure and evasion. Concurrent adaptive activation of immune regulator components (tumor infiltrating cells) and downstream signaling pathways (PI3K-AKT and MAPK signaling) enhances the rewiring of a hostile tumour microenvironment. The complexity crosstalk of the signalling pathways and immune infiltration cluster deserve attention to override TNBC chemoresistance. Therefore, this review aims to highlight an overview on the molecular crosstalk (BRCA, PI3K-AKT, TP53 and MAPK signaling) with immune response as a potential integrative therapeutic option to TNBC chemoresistance.