Table 2.

Examples of BC therapies that might benefit from NORAD depletion.

Therapy	BC Application	Mechanism of Action	Barriers to Therapy Response	Potential Impact of NORAD Depletion	Impact of NORAD Depletion in Therapy Response	References
PARP inhibitors	BRCA mutations	Impairment of SSB repair	Restoration of HR	Improved PARP downregulation and impairment of DDR	Inhibition of tumor cell growth and proliferation	[52]
DNA damage-inducing chemotherapy	First-line therapy	DNA damage leads to apoptosis and inhibition of proliferation	DNA damage repair and resistance to therapy	Potential synergistic effect on FOXO1 downregulation	Reinforcement of apoptosis and inhibition of proliferation	[113]
FOXO1 inhibitor (AS1842856)	BL tumors	FOXO1 pathway inhibition	Inhibitor does not bind to the phosphorylated form of FOXO1	Potential synergistic effect on downregulating FOXO1 and its phosphorylated form	Reinforcement of apoptosis and inhibition of proliferation	[114]
PAM inhibitors combined with CDK4/6 inhibitors	ER+ tumors	PAM downregulation leads to the diminished capability of BC to acquire resistance to endocrine therapy	Acquired resistance to endocrine therapy	mTOR inhibition	Improved sensitization of tumor cells to endocrine therapy	[115]
PAM inhibitors combined with anti-HER2 antibodies	HER2+ tumors	PAM downregulation sensitizes to anti-HER2 antibodies	Acquired resistance to HER2 antibodies	Synergistic effect on downregulating PAM	Improved sensitization of tumor cells to HER2 antibodies	[115]
Doxorubicin	First-line therapy	DNA DSB and activation of RhoA/MLC pathway	Promotes migration and invasion via RhoA/MLC pathway	Impairment of DNA damage repair machinery	Decreased tumor cell survival and inhibition of migration and invasion	[116]

DDR—DNA damage repair; DSB—double-strand break; HR—homologous repair; SSB—single-strand break.