TABLE 1.
HDACs regulate the resistance to therapies in lung cancer.
| Class HDAC, I, IIa, IIb and III | Biological Function/cancer hallmarks clinical impact | Target/signaling pathways | Resistance/sensitivity therapies | HDACs inhibitors promote sensitivity | In vitro, in vivo and clinical trials | Reference |
|---|---|---|---|---|---|---|
| HDAC-1 | Cell proliferation and migration, | HDAC/RXR/HtrA1 | Cisplatin resistance | Panobinostat (LBH-589), Vorinostat (SAHA), CG347B | A549, H460, H1299, Balb/c-nu mice | Wang et al. (2020b) |
| HDAC-1 | tumor progression, poor survival | CHK1, E-cadherin | Erlotinib resistance | Panobinostat | Clinical phase 1, (EGFR-mutant NSCLC patients) | Gray et al. (2014) |
| HDAC-1, -2, -4 | Epithelial-to-mesenchymal transition (EMT) | CREBBP, CDH1 | Pracinostat | H1882, DMS53, 293FT, Athymic Foxn1nu mice | Jia et al. (2018) | |
| HDAC-1 | Apoptosis inhibition | BAX-Ku70 interaction | Amphiregulin Promotes Resistance to Gefitinib | TSA, SAHA | H358 and H322, NMRI nude mice | Busser et al. (2010) |
| HDAC-1 | Apoptosis inhibition, poor prognosis, tumor recurrence | C/EBP-β/TRIB1/HDAC/p53 axis | Cisplatin, doxorubicin resistance | SAHA | H460, A549 and H1299, xenograft model mice | Wang et al. (2017) |
| HDAC-1 | Apoptosis inhibition | BIM | Gefitinib and erlotinib resistance | SAHA | PC-3, PC-9, HCC827, and HCC2279, BALB/cAJcl-nu/nu mice | Nakagawa et al. (2013) |
| HDAC-1, -2, –3 | Apoptosis inhibition, promote cell cycle | p21-cyclin B1 | Gefitinib resistance | TSA, SAHA + combination with Silibinin | H1299, H358, and H322, athymic (nu/nu) nude mice | Mateen et al. (2012) |
| HDAC-1, -2, –3 | Apoptosis inhibition | FLIP | Cisplatin-resistant | SAHA, LBH-589 | H460, A549 and 34LU | Riley et al. (2013) |
| HDAC-6 | Inhibited proliferation, induce apoptosis | EGFR | Gefitinib resistance | CAY10603 | A549, HCC827 and H1975 | Wang et al. (2016b) |
| HDAC-1, -2, -3 | Radiosensitization, induce apoptosis | FLIP and caspase-8 | Resistance to Radiation | SAHA | A549, H460, H1373 CCD34Lu and HCC15 | McLaughlin et al. (2016) |
| HDAC-1, -3, -6, -8 | Apoptosis inhibition cell proliferation migration, invasión, | p21 | Paclitaxel resistance | SAHA, SNOH-3 | A549 and NCI-H1299, and HUVEC, SCID mice | Wang et al. (2016a) |
| HDAC-1 | Growth inhibition, induce apoptosis | EGFR | Erlotinib resistance | SAHA, MPT0E028 | CL97, A549, H1975, and H1299, nude-athymic mice | Chen et al. (2013) |
| HDAC-1, -2 | DNA repair inhibition, promote growth size tumor | ACTL6A | Cisplatin resistance | Panobinostat | A549, H1299, NOD scid IL2 receptor g chain knockout (NSG) mice | Xiao et al. (2021) |
| HDAC-1 | Poor prognosis, induced tumor cell growth | HDAC/OAZ1 axis | Cisplatin resistance | S11 | A549, NCI-H460, and NCI-H1299, BALB/c nude mice | Sun et al. (2019) |
| HDAC-1 | EMT | ALK | Crizotinib, alectinib, lorlatinib and ceritinib resiistance | SAHA | PF240-PE, PF240, PF240-PC, PF521 | Stockhammer et al. (2020) |
| HDAC-1 | Apoptosis inhibition, cell proliferation | PTEN | Erlotinib resistance | SAHA | PC-9, PC-9/ER, H1975 | Wu et al. (2020) |
| HDAC-3 | Apoptosis inhibition | BIM | Osimertinib resistance | SAHA | PC-9 and PC-3, BALB/c-nu/nu mice | Tanimoto et al. (2017) |
| Pan-HDAC | Cell proliferation, apoptosis inhibition | EGFR | Carboplatin resistance | Panobinostat | A549, Calu-1, H226, H460, H838 and SKMES-1, NOD-SCID xenograft mice | Wang et al. (2018b) |
| HDAC-1 | Apoptosis inhibition and autophagy | EGFR | Gefitinib and erlotinib resistance | SAHA | PC-9, H1975, athymic nude mice | Lee et al. (2015) |
| HDAC-1, -2 | Promotecell growth and cell proliferation, apoptosis inhibition | EGFR | Erlotinib resistance | YF454A | A549, H1299, H1975, PC9, HCC827, BALB/cA nude mice | Yu et al. (2017) |
| HDAC-1, -4 | Induced cell proliferation, apoptosis inhibition | HIF-1α | Cisplatin resistant | panobinostat | NCI-H23, A549 | Fischer et al. (2015) |
| HDAC I/IV | Inhibit an efective antigen-specifc immune response | PDL-1 | PDL-1 immunotherapy | Mocetinostat is a spectrum-selective inhibitor | NCI-H23, NCI-H1299, NCI-H1437, NCIH1703, NCI-H1792, NCI-H1838, NCI-H2122 and CT26. WT (CT26). | Briere et al. (2018) |
| HDAC-2 | Promote resistance to therapy | ABCA1 | Cisplatin resistant | Valproic acid (VPA) | A549, H358 | Chen et al. (2017b) |
| HDAC-1, -2, -3 | Induced cell cycle and decreased apoptotic | Inhibit the PI3K/AKT and RAS/MAPK pathways | Icotinib resistant | chidamide | A549, HCC827, HCC827IR, Bagg Albino (BALB/c) athymic nude mice | Zhang et al. (2019) |
| HDAC | Promote Cell cycle apoptosis inhibition, decreased DNA damage repair activity | FoxM1 and MYC | Olaparib resistant | CUDC-907 | DMS273, H82, H526, H69, and H446, patient-derived xenografts (PDXs) model | Ma et al. (2021) |
| HDAC-1,- 2,- 3, -6, | Promotion of tumor growth | BET | Osimertinib resistance | SAHA, TSA | H1975 and HCC827, athymic (nu/nu) mice | Meng et al. (2021) |
| SIRT1 | Induces cell cycle, proliferation, and apoptosis is suppressed in cisplatin-resistant cells. | p53, p21, | Cisplatin resistant | A549 and A549/CADD cells, | Yu et al. (2020) | |
| SIRT1 | Induced apoptosis resistance and chemoresistance | β-TrCP- XRCC1 | Cisplatin resistant | EX-527 | H460 | Yousafzai et al. (2019) |
| SIRT5 | Regulates drug resistance, poor overall- and disease-free survival | Nrf2 | Cisplatin resistant | A549, LU99 and NCI-H460, nu/nu mice | Lu et al. (2014) |
Refs (Busser et al., 2010; Mateen et al., 2012; Chen et al., 2013; Nakagawa et al., 2013; Riley et al., 2013; Gray et al., 2014; Lu et al., 2014; Fischer et al., 2015; Lee et al., 2015; Wang L. et al., 2016; Wang et al., 2016b; McLaughlin et al., 2016; Chen J. H. et al., 2017; Tanimoto et al., 2017; Wang et al., 2017; Yu et al., 2017; Briere et al., 2018; Wang L. et al., 2018; Jia et al., 2018; Wei et al., 2018; Sun et al., 2019; Yousafzai et al., 2019; Zhang et al., 2019; Wang W. et al., 2020; Stockhammer et al., 2020; Wu et al., 2020; Yu et al., 2020; Ma et al., 2021; Meng et al., 2021; Xiao et al., 2021).