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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]