Table 2 Examples of drugs used in HER2 breast cancer treatment

Trastuzumab (Herceptin)

Monoclonal antibody against HER2

FDA approved

[355,356,357,358,359,360]

Ado trastuzumab emtansine (T-DM1)

Bifunctional antibody-drug (trastuzumab linked to ematansine, DM1). Binds HER2 and inhibits microtubule assembly/disassembly

FDA approved

[361,362,363,364]

Eetumaxomab

Monoclonal antibody with CD3 and HER2 recognition sites

Clinical trial

[365, 366]

Pertuzumab (Perjeta)

Recombinant humanized antibody against domain II of HER2

FDA approved

[284, 367, 368]

MM-111

Antibody against HER2-HER3 dimers

Clinical trial

[369, 370]

Lapatinib (Tykerb)

Irreversible tyrosine kinase inhibitor in luminal B cancers

FDA approved

[371, 372]

Afatinib

Irreversible pan-HER tyrosine kinase inhibitor

Clinical trial

[373,374,375]

Canertinib

Irreversible tyrosine kinase inhibitor

Clinical trial

[19, 376, 377]

Neratinib

Irreversible pan-HER tyrosine kinase inhibitor, effective against EGFR, HER2, and HER4

Clinical trial

[378,379,380,381]

Gefitinib

EGFR tyrosine kinase inhibitor

Clinical trial

[382, 383]

Erlotinib hydrochloride (Erlotinib)

Reversibly binds to the intracellular catalytic domain of EGFR; used also in TBNC cancers

Clinical trial

[383,384,385]

Sapitinib

Tyrosine kinase inhibitor effective in luminal B resistant cells

Clinical trial

[380, 386]

Sorafenib

Blocks the enzyme RAF kinase, inhibiting cancer cell proliferation and autophagy induction

Clinical trial

[63,388,, 387–389]

Sildenafil citrate

Selectively inhibits cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase

Clinical trial

[63]

MM-121

Human monoclonal antibody against HER3

Clinical trial

[267,391,, 390–392]

MM-302

Doxorubicin encapsulated within liposomes, and conjugated to a monoclonal antibody against HER2. Inhibits HER2 and topoisomerase II

Clinical trial

[393, 394]

ARRAY-380

Reversible selective HER2 inhibitor

Clinical trial

[395]

TAK-285

HER2-EGFR tyrosine kinase inhibitor

HER2-positive breast cancer cells

[396,397,398,399]

Everolimus (Afinitor)

Inhibitor of mTORC1 used both in luminal A and in HER2-positive tumors

FDA approved

[277,278,279, 283]

Temsiroliums

Inhibitor of mTORC1 used in luminal A, TNBC, and HER2-positive tumors

Clinical trial

[331]

GDC-0941

PI3K inhibitor

Clinical trial

[400, 401]

SAR245408

PI3K inhibitor

Clinical trial

[402, 403]

17-AAG

Hsp90 inhibitor

Clinical trial

[404,405,406]

Retaspinmycin (IPI-504)

Hsp90 inhibitor

Clinical trial

[406,407,408]

Genetespib

Hsp90 inhibitor used in metastatic HER2 breast cancers

Clinical trial

[409,410,411,412]

Pazopanib

inhibitor of VEGFRs able to inhibit Hsp90 ATPase activity

Clinical trial

[63, 413, 414]

SNX-2112

Hsp90 inhibitor, effective in HER2 and luminal B breast cancers

Clinical trial

[83, 280, 415]

Geldanamycin

Hsp90 inhibitor

HER2-positive breast cancer cells

[20,115,, 109, 114–116]

KIN001-51

HER3 binder, impairs dimerization

HER2-positive breast cancer cells

[416, 417]

TX1-85-1

Induces HER3 degradation by covalent binding to a residue in the receptor

HER2-positive breast cancer cells

[100, 383]

TX2-121-1

Derivate of TX1-85-1 linked to adamantane group. Induces HER3 degradation

HER2-positive breast cancer cells

[100, 383]

Patritumab (AMG 888)

Monoclonal antibody directed against the ligand-binding pocket of HER3

Clinical trial

[418]

MEHD7945A

Monoclonal antibody directed against EGFR and HER3

Clinical trial

[419, 420]

Pilaralisib

Pan-class I PI3K inhibitor

HER2-positive breast cancer cells

[224, 421]

liposomal paclitaxel

Inhibits tubulin assembly/disassembly

FDA approved

[224, 421, 422]

hydroxychloroquine

Autophagy inhibitor, suppresses lysosomal acidification

Clinical trial

[167, 225]

Eeyarestatins

p97 inhibitor

HER2-positive breast cancer cells

[81, 85]

NMS-873

p97 inhibitor

HER2-positive breast cancer cells

[81]

HA15

Inhibitor of BiP ATPase activity

HER2-positive breast cancer cells

[173]