Fig. 2

A Combined inhibition of Poly (ADP-ribose) polymerase (PARP) by Talazoparib (TAL) and phosphatidylinositol 3-kinase (PI3K) by LY294002 synergistically inhibited the proliferation of BRCA1 mutant HCC1937 triple-negative breast cancer (TNBC) cells. This figure illustrates the enhanced anti-proliferative effects of the combination treatment compared to each drug alone. The combined inhibition induced multiple cellular responses, including apoptosis, G0/G1 arrest, oxidative stress, and increased DNA damage. The synergistic effect suggests that the dual targeting strategy holds promise as a therapeutic approach for TNBC with BRCA1 mutations. B LAR (Luminal Androgen Receptor) subtype patient-derived xenografts (PDXs) of triple-negative breast cancer (TNBC) exhibited a significant enrichment of PIK3CA and AKT1 mutations, along with higher levels of luminal-androgen-like gene expression and increased activation of the PI3K pathway proteins, when compared to other TNBC subtypes. Immunohistochemistry analysis revealed strong expression of luminal cytokeratin CK18 and androgen receptor (AR) in three LAR PDX models. In vivo experiments using these PDX models, which harbored genomic alterations of PIK3CA and AKT1 and were resistant to the AR antagonist enzalutamide, demonstrated that mTOR and PI3K inhibitors displayed notable antitumor activity