From: Approaches to modernize the combination drug development paradigm
Types of combinations | Examples |
---|---|
(1) Synergistic or additive combinations | |
Targeting the same molecule for maximal target inhibition | Dual human epidermal growth factor receptor 2 (HER2) blockade (pertuzumab and trastuzumab in HER2-amplified breast cancer) [23, 25] |
Vertical targeting: inhibiting two or more targets along the same pathway | BRAF and MEK inhibition (vemurafenib and cobimetinib, dabrafenib, and trametinib in melanoma) [27, 29] |
Horizontal targeting: inhibiting parallel or compensatory pathways | Phosphoinositide 3-kinase (PI3K) and MEK inhibition (BKM120 and trametinib in RAS- or BRAF-mutant solid tumors) [128] |
(2) Synthetic lethality | Poly(ADP-ribose) polymerase (PARP) inhibitor and DNA-damaging agent (veliparib plus platinum-based chemotherapy in triple-negative breast cancer) (NCT02032277) |
(3) Reversal of resistance | Cyclin-dependent kinase (CDK) and estrogen receptor (ER) inhibition (palbociclib and fulvestrant in hormone-receptor-positive breast cancer in postmenopausal women) [30] |