Table 1. Schematic representation of rational combination PI3K inhibitors with other therapeutics in breast cancer.
| Combination therapeutic strategies | Applied drugs | Type of study | Tpye of breast cancer | Reference |
|---|---|---|---|---|
| PI3K and RTK inhibitors | p110-selective inhibitor (BYL719) & HER3-neutralizing antibody (LJM716) | in vitro and in vivo | HER2-posotive breast cancer | Garrett et al. (2013) |
| PI3K inhibitor (GDC-0941) & dual EGFR and HER3 inhibitor (MEHD7945A) | in vitro and in vivo | Triple-negative breast cancer | Tao et al. (2014) | |
| AKT inhibitor (MK-2206) & HER2 inhibitor (trastuzumab) | Phase I trial | HER2-posotive breast cancer | Hudis et al. (2013) | |
| PI3K inhibitor (BKM120/buparlisib) & HER2 inhibitor (trastuzumab) | Phase IB trial | HER2-positive advanced or metastatic breast cancer | Saura et al. (2014) | |
| PI3K inhibitor (buparlisib) & HER2 inhibitor (lapatinib) | Phase IB trial | HER2-positive advanced breast cancer | Guerin et al. (2017) | |
| PI3K inhibitor (BKM120/buparlisib) & HER2 inhibitor (trastuzumab) | Phase II trial | HER2-positive locally advanced or metastatic breast cancer | Pistilli et al. (2018) | |
| PI3K inhibitors and endocrine therapy | PI3K inhibitor (pictilisib) & ER antagonist (fulvestrant) | Randomized double-blind phase II trial | ER-positive, HER2-negative metastatic breast cancer | Krop et al. (2016) |
| PI3K inhibitor (pictilisib) & aromatase inhibitor (anastrozole) | Phase II randomized preoperative window-of-opportunity study | ER-positive breast cancer | Schmid et al. (2016) | |
| PI3K inhibitor (buparlisib) & ER antagonist (fulvestrant) | Randomized double-blind placebo-controlled phase III trial | ER-positive HER2-negative advanced breast cancer | Baselga et al. (2017) | |
| PI3K inhibitor (buparlisib) & ER antagonist (fulvestrant) | Randomized double-blind placebo-controlled phase III trial | ER-positive HER2-negative advanced breast cancer progressing on or after mTOR inhibition | Di Leo et al. (2018) | |
| p110-selective inhibitor & ER antagonist (fulvestrant) | Phase III trial | HR-positive or OR-positive HER2-negative advanced breast cancer progressing on or after mTOR aromatase inhibitor | ongoing trial | |
| PI3K and PARR inhibitors | PI3K inhibitor (NVP-BKM120) & PARP inhibitor (Olaparib) | in vivo | BRCA1-related breast cancer | Juvekar et al. (2012) |
| PI3K inhibitor (BKM120) & PARP inhibitor (Olaparib) | in vitro and in vivo | BRCA-proficient triple-negative breast cancer | Ibrahim et al. (2012) | |
| Dual PI3K and mTOR inhibitor (GDC-0980) & PARP inhibitor (ABT888) | in vitro and in vivo | Triple negative breast cancer | De et al. (2014) | |
| PI3K inhibitor (BKM120) & PARP inhibitor (Olaparib) | Phase I trial | High-grade breast cancer | Matulonis et al. (2017) | |
| PI3K inhibitors and immune checkpoint targeting agents | PI3K-inhibiting supramolecule & anti-PD-1 antibody | in vivo | 4T1 breast cancer | Kulkarni et al. (2016) |
| PI3Kγ inhibitor (TG100-115) & anti-PD-1 antibody (clone RPM1-14)/anti-CTLA4 antibody (clone 9H10) | in vivo | 4T1 breast cancer | De Henau et al. (2016) | |
| PI3K inhibitor (BKM120) & anti-PD-1 antibody | in vivo | 4T1/PyMT breast cancer patient-derived triple negative breast cancer | Sai et al. (2017) |
Notes:
PI3K, phosphatidylinositol 3-kinase; RTK, receptor tyrosine kinase; HER3, epidermal growth factor receptor 3; EGFR, epidermal growth factor receptor; ER, estrogen receptor; PARP, poly-ADP-ribosylation; mTOR, Mammalian target of rapamycin; HER2, epidermal growth factor receptor 2.