Skip to main content

Table 1 Types of combinations

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]