Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer

Table 1 Molecular biomarkers associated with the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathway in triple negative breast cancer

Biomarkers class	Biomarkers name	Mechanism of action/inhibition	Ref.
Protein biomarkers	TYMS	Knockdown of TYMS leads to downregulation of mTOR, p-PI3K, and p-AKT expressions, inhibits cell proliferation and migration, while promoting apoptosis	[20]
	GBP2	GBP2 overexpression collaborates with autophagy-related protein 2 to inhibit the PI3K/Akt/mTOR pathway, thereby enhances the sensitivity of TNBC cells to paclitaxel	[29]
	ACTL8	Facilitate the proliferation, migration, and invasion of TNBC cells by activating the PI3K/Akt/mTOR signaling pathway while suppressing apoptosis	[30,31]
	OPN	Activate PI3K/Akt/mTOR pathway to regulate anti-lipid peroxidation mediated by GPX4, thereby promoting tumor growth and metastasis in TNBC	[38]
mRNA biomarkers	ROR2	Downregulation of ROR2 augments chemical sensitivity towards adriamycin; upregulation of ROR2 activates the PI3K/Akt/mTOR signaling pathway to facilitate TNBC metastasis	[43]
Non-coding RNA markers	Linc00707	Competitively bind to miR-423-5p to up-regulate MARCH2 expression, promote TNBC progression and autophagy through the PI3K/Akt/mTOR pathway	[45]
	MiR-145	Decreasing in miR-145 attenuates PI3K activation by inhibiting the MAPK signaling pathway, thereby diminishing AKT and mTOR activity	[48]
Transcription factor	Nrf3	The overexpression of Nrf3 activates the PI3K/Akt/mTOR signaling pathway and regulates the expression of proteins associated with EMT	[23]

TYMS: Thymidylate synthase; GBP2: Guanylate-binding protein 2; ACTL8: Actin-like protein 8; OPN: Osteopontin; ROR2: Receptor tyrosine kinase-like orphan receptor 2; Nrf3: Nuclear factor erythroid-2-like factor 3; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B; mTOR: Mechanistic target of rapamycin; TNBC: Triple negative breast cancer; GPX4: Glutathione peroxidase 4; MARCH2: Membrane-associated RING finger protein 2; MAPK: Mitogen-activated protein kinase; EMT: Epithelial-mesenchymal transition.