The PIK3CA gene and its pivotal role in tumor tropism of triple-negative breast cancer

Abstract

The PIK3CA gene is a linchpin in the intricate molecular network governing triple-negative breast cancer (TNBC) tumor tropism, serving as a focal point for understanding this aggressive disease. Anchored within the PI3K/AKT/mTOR signaling axis, PIK3CA mutations exert substantial influence, driving cellular processes that highlight the unique biology of TNBC. This review meticulously highlights the association between PIK3CA mutations and distinct TNBC subtypes, elucidating the gene's multifaceted contributions to tumor tropism. Molecular dissection reveals how PIK3CA mutations dynamically modulate chemokine responses, growth factor signaling, and extracellular matrix interactions, orchestrating the complex migratory behaviour characteristic of TNBC cells. A detailed exploration of PIK3CA-targeted strategies in the therapeutic arena is presented, outlining the current landscape of clinical trials and precision medicine approaches. As the scientific narrative converges, this review underscores the critical role of PIK3CA in shaping the molecular intricacies of TNBC tumor tropism and illuminates pathways toward tailored interventions, promising a paradigm shift in the clinical management of TNBC.

Keywords: EMT; Metastasis; PI3K; PI3K/AKT/mTOR pathway; Targeted therapy; Triple negative breast cancer; Tumor tropism.

Graphical abstract

Fig. 1

Mutational spectrum of PIK3CA in TNBC subtypes. This figure illustrates the protein domains of PIK3CA and highlights the positions of specific mutations commonly found in TNBC subtypes. The most frequent mutation type in each domain is labeled, with red dots representing missense mutations.

Fig. 2

PI3K and PIP2-mediated pathway. This figure depicts the PI3K-mediated phosphorylation of PIP2 to PIP3, which activates downstream effectors, including AKT. These effectors are crucial for promoting cell survival, growth, and migration in TNBC cells.

Fig. 3

Overview of the PI3K/AKT/mTOR signaling pathway. This figure overviews the PI3K/AKT/mTOR signaling pathway, activated by estrogen and receptor tyrosine kinases. Key activating nodes (AKT, Rheb, mTORC1, and mTORC2) and negative regulators (PTEN, TSC complex) are highlighted. The figure also illustrates the crosstalk with the RAS and LKB1/AMPK pathways.