. 2020 Dec 2;25(23):5686. doi: 10.3390/molecules25235686

Table 2.

Inhibitors and immunomodulators used in breast cancer therapy.

	Approved Agents	Molecular Targets	Mechanism of Action	Ref.
EGFR Inhibitors	Afatinib	Inhibits EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) receptors	Irreversibly binds to members of the ErbB receptor family	[78]
	Lapatinib		Inhibit the intracellular phosphorylation of tyrosine kinase associated with both wild-type and mutation EGFR	[57,79]
	Erlotinib	Inhibitor of EGFR tyrosine kinase		[77,80]
	Gefitinib	Inhibitor of EGFR tyrosine kinase	Selectively binds to the EGFR-tyrosine kinase domain, preventing ATP from binding and blocking subsequent receptor autophosphorylation	[81]
	Dacomitinib	Inhibitor of the activity of the human EGFR family	Inhibition via irreversible binding at the ATP domain of the EGFR proteins (EGFR/HER1, HER2, and HER4)	[82]
	Neratinib	Inhibitor of the activity of the human EGFR family	Irreversibly binds to Cys-773 and Cys-805 of the ATP-binding domain of EGFR proteins (EGFR/HER1, HER2, and HER4), as well as downstream pathways including ERK and Akt.	[83]
	Osimertinib	Inhibitor of specific mutated forms of EGFR, including T790M, L858R, and exon 19 deletion	Irreversibly binds to Cys-797 of certain mutant forms of EGFR (L858R, exon 19 deletion, and double mutants containing T790M	[84]
EGFR Inhibitors		HER-2, HER-3, and HER-4. EGFR, ErbB-4,	Downregulates ErbB signaling	[85]
			PI3K/Akt/
			Directed against the ErbB family of receptors	[86]
PI3K/AKT/mTOR pathway inhibitors	Buparlisib	pan-class I phosphoinositide 3-kinase isoforms inhibitor	Specifically inhibits class I PI3K and tubulin	[87]
	Alectinib	Tyrosine kinase inhibitor of ALK and RET proteins	electively inhibits the activity of ALK tyrosine kinase and tyrosine-protein kinase receptor RET.	[88]
	Crizotinib	Multikinase inhibitor	Competitively binds to the ATP-binding pocket of many receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), reactive oxygen species 1 (ROS1), and Recepteur d’Origine Nantais (RON)	[89]
	Ceritinib	Potent inhibitor of ALK	Blocks autophosphorylation of ALK, which inhibits downstream signaling proteins.	[90]
Ras/Raf/MEK/ERK signaling pathway Inhibitors	Sorafenib	Multikinase inhibitor	Protein kinase inhibitor of many proteins, including VEGFR, PDGFR, and RAF kinases.	[91]
	Vemurafenib	Inhibition of the mutated BRAF V600E kinase	Inhibits a serine-threonine protein kinase B-RAF	[92]
	Dabrafenib (TAFINLAR^®)	Inhibitor of B-raf protein	Inhibitor of the B-RAF and C-RAF proteins through ATP competitive binding of the active conformation of BRAF kinase	[93]
	Trametinib (Mekinist^®)	Reversible allosteric inhibitor of MEK1 and MEK2 activity	It is an ATP non-competitive inhibitor that binds MEK adjacent to the ATP binding site in common with other MEK allosteric inhibitor	[94]
Immunomodulators	Nivolumab (Opdivo^®)	MoAbs that bind to the PD-1 receptor	Bind to the PD-1 receptor and block its interaction with PD-L1 and PD-L2	[95,96,97,98,99]
	Pembrolizumab (Keytruda^®)	MoAbs that bind to the PD-1 receptor		[95,96,98,100]
	Durvalumab (Imfinzi^®)	MoAbs that block the interaction of PD-L1	Block the interaction of PD-L1 with PD-1 and CD80 (B7. 1) to release the inhibition of immune responses.	[95,101,102,103]
	Atezolizumab (Tecentriq^®)			[104,105]
	Avelumab (Bavencio^®)			[106]
	Ipilimumab (Yervoy^®)	MoAbs that bind to the CTLA-4 receptor	Binds to CTLA-4, blocking the inhibitory signals of T-cell inactivation.	[95,96,97,101,106,107]
	Tremelimumab	MoAbs that bind to the CTLA-4 receptor		[95,101,102]