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Review

Role Of Epigenetic Drugs In Sensitizing Cancers To Anticancer Therapies: Emerging Trends And Clinical Advancements

ORCID Icon, ORCID Icon & ORCID Icon
Pages 517-537 | Received 20 Apr 2023, Accepted 25 May 2023, Published online: 14 Jun 2023

References

  • Thurn KT , ThomasS , MooreA , MunsterPN. Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer. Future Oncol.7(2), 263–283 (2011).
  • Zwergel C , ValenteS , MaiA. DNA methyltransferases inhibitors from natural sources. Curr. Top. Med. Chem.16(7), 680–696 (2016).
  • Esteller M . Epigenetics in cancer. N. Engl. J. Med.358(11), 1148–1159 (2008).
  • Simó-Riudalbas L , EstellerM. Cancer genomics identifies disrupted epigenetic genes. Hum. Genet.133(6), 713–725 (2014).
  • Singh D , KhanMA , SiddiqueHR. Emerging role of long non-coding rnas in cancer chemoresistance: unravelling the multifaceted role and prospective therapeutic targeting. Mol. Biol. Rep.47(7), 5569–5585 (2020)
  • Fatma H , MauryaSK , SiddiqueHR. Epigenetic modifications of c-MYC: role in cancer cell reprogramming, progression and chemoresistance. Semin. Cancer Biol.83, 166–176 (2022).
  • Simó-Riudalbas L , EstellerM. Targeting the histone orthography of cancer: drugs for writers, erasers and readers. Br. J. Pharmacol.172(11), 2716–2732 (2015).
  • Ahuja N , SharmaAR , BaylinSB. Epigenetic therapeutics: a new weapon in the war against cancer. Annu. Rev. Med.67, 73–89 (2016).
  • Merchant SL , CulosK , WyattH. Ivosidenib: IDH1 inhibitor for the treatment of acute myeloid leukemia. J. Adv. Pract. Oncol.10(5), 494–500 (2019)
  • Stathis A , ZuccaE , BekraddaMet al. Clinical response of carcinomas harboring the BRD4-NUT oncoprotein to the targeted bromodomain inhibitor OTX015/MK-8628. Cancer Discov.6(5), 492–500 (2016).
  • Ravindran Menon D , HammerlindlHet al. Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer. Theranostics.10(14), 6261–6277 (2020).
  • Siddique HR , SaleemM. Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem Cells.30(3), 372–378 (2012).
  • Li Y , WangZ , AjaniJA , SongS. Drug resistance and cancer stem cells. Cell Commun. Signal.19(1), 19 (2021)
  • Inbar-Feigenberg M , ChoufaniS , ButcherDTet al. Basic concepts of epigenetics. Fertil. Steril.99(3), 607–15 (2013).
  • Ferreira HJ , EstellerM. CpG islands in cancer: heads, tails, and sides. Methods Mol. Biol.1766, 49–80 (2018).
  • Ho AS , TurcanS , ChanTA. Epigenetic therapy: use of agents targeting deacetylation and methylation in cancer management. Oncol. Targets Ther.6, 223–32 (2013).
  • Pappalardo XG , BarraV. Losing DNA methylation at repetitive elements and breaking bad. Epigenetics Chromatin.14(1), 25 (2021).
  • Liao J , KarnikR , GuHet al. Targeted disruption of DNMT1, DNMT3A, and DNMT3B in human embryonic stem cells. Nat. Genet.47(5), 469–78 (2015).
  • Villicaña S , BellJT. Genetic impacts on DNA methylation: research findings and future perspectives. Genome Biol.22(1), 127 (2021).
  • Majchrzak-Celińska A , PaluszczakJ , SzalataMet al. The methylation of a panel of genes differentiates low-grade from high-grade gliomas. Tumour Biol.36(5), 3831–41 (2015).
  • Cheng Y , HeC , WangMet al. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct. Target Ther.4, 62 (2019).
  • Jones PA , OhtaniH , ChakravarthyA , DeCarvalho DD. Epigenetic therapy in immune-oncology. Nat. Rev. Cancer.19(3), 151–161 (2019).
  • Hu C , LiuX , ZengYet al. DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application. Clin. Epigenetics13(1), 166 (2021).
  • Ishak CA , ClassonM , DeCarvalho DD. Deregulation of retroelements as an emerging therapeutic opportunity in cancer. Trends Cancer4(8), 583–597 (2018).
  • Roulois D , LooYau H , SinghaniaRet al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell.162(5), 961–73 (2015).
  • Wong KK , LawrieCH , GreenTM. Oncogenic roles and inhibitors of DNMT1, DNMT3A, and DNMT3B in acute myeloid leukaemia. Biomark Insights14, 1177271919846454 (2019).
  • Akone SH , Ntie-KangF , StuhldreierFet al. Natural products impacting DNA methyltransferases and histone deacetylases. Front. Pharmacol.11, 992 (2020).
  • Hontecillas-Prieto L , Flores-CamposR , SilverAet al. Synergistic enhancement of cancer therapy using HDAC inhibitors: opportunity for clinical trials. Front. Genet.11, 578011 (2020).
  • Ceccacci E , MinucciS. Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia. Br. J. Cancer114(6), 605–11 (2016).
  • Mrakovcic M , FröhlichLF. Molecular determinants of cancer therapy resistance to HDAC inhibitor-induced autophagy. Cancers (Basel).12(1), 109 (2019).
  • Patnaik S , Anupriya . Drugs targeting epigenetic modifications and plausible therapeutic strategies against colorectal cancer. Front. Pharmacol.10, 588 (2019).
  • Banik D , MoufarrijS , VillagraA. Immunoepigenetics combination therapies: an overview of the role of HDACs in cancer immunotherapy. Int. J. Mol. Sci.20(9), 2241 (2019).
  • Mann BS , JohnsonJR , CohenMHet al. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist.12(10), 1247–52 (2007).
  • Lu Y , ChanYT , TanHYet al. Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol. Cancer.19(1), 79 (2020).
  • Losson H , SchnekenburgerM , DicatoM , DiederichM. Natural compound histone deacetylase inhibitors (HDACi): synergy with inflammatory signaling pathway modulators and clinical applications in cancer. Molecules.21(11), 1608 (2016).
  • Han D , HuangM , WangTet al. Lysine methylation of transcription factors in cancer. Cell Death Dis.10(4), 290 (2019).
  • Marcos-Villar L , NietoA. The DOT1L inhibitor pinometostat decreases the host-response against infections: considerations about its use in human therapy. Sci. Rep.9(1), 16862 (2019).
  • Yi Y , GeS. Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias. J. Hematol. Oncol.15(1), 35 (2022)
  • Buocikova V , Rios-MondragonI , PilalisEet al. Epigenetics in breast cancer therapy – new strategies and future nanomedicine perspectives. Cancers (Basel).12(12), 3622 (2020)
  • Lazo PA . Targeting histone epigenetic modifications and DNA damage responses in synthetic lethality strategies in cancer?Cancers (Basel).14(16), 4050 (2022).
  • Capobianco E , MoraA , LaSala Det al. Separate and combined effects of DNMT and HDAC inhibitors in treating human multidrug-resistant osteosarcoma HosDXR150 cell line. PLOS ONE.9(4), e95596 (2014).
  • Wang N , ZhangH , YaoQet al. TGFBI promoter hypermethylation correlating with paclitaxel chemoresistance in ovarian cancer. J. Exp. Clin. Cancer Res.31(1), 6 (2012).
  • Kim J , JangG , SimSHet al. SMARCA4 depletion induces cisplatin resistance by activating YAP1-mediated epithelial-to-mesenchymal transition in triple-negative breast cancer. Cancers (Basel).13(21), 5474 (2021).
  • Tian Y , XuL , LiXet al. SMARCA4: current status and future perspectives in non-small-cell lung cancer. Cancer Lett.554, 216022 (2023).
  • Moufarrij S , DandapaniM , ArthoferEet al. Epigenetic therapy for ovarian cancer: promise and progress. Clin. Epigenetics11(1), 7 (2019).
  • Matei D , FangF , ShenCet al. Epigenetic resensitization to platinum in ovarian cancer. Cancer Res.72(9), 2197–205 (2012).
  • Glasspool RM , BrownR , GoreMEet al. A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in combination with carboplatin vs. carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer. Br. J. Cancer.110(8), 1923–9 (2014).
  • Kwon NH , KimJS , LeeJYet al. DNA methylation and the expression of IL-4 and IFN-gamma promoter genes in patients with bronchial asthma. J. Clin. Immunol.28(2), 139–46 (2008).
  • Nogales V , ReinholdWC , VarmaSet al. Epigenetic inactivation of the putative DNA/RNA helicase SLFN11 in human cancer confers resistance to platinum drugs. Oncotarget.7(3), 3084–97 (2016).
  • Liang J , LuT , ChenZet al. Mechanisms of resistance to pemetrexed in non-small cell lung cancer. Transl. Lung Cancer Res.8(6), 1107–1118 (2019).
  • Peng Q , WengK , LiSet al. A perspective of epigenetic regulation in radiotherapy. Front. Cell Dev. Biol.9, 624312 (2021).
  • Thotala D , KarvasRM , EngelbachJAet al. Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal neurons and sensitizing malignant glioblastoma cells. Oncotarget.6(33), 35004–35022 (2015).
  • Wang J , ZhouF , LiZet al. Pharmacological targeting of BET proteins attenuates radiation-induced lung fibrosis. Sci. Rep.8(1), 998 (2018).
  • Chan E , ArlinghausLR , CardinDBet al. Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer. Radiother. Oncol.119(2), 312–8 (2016).
  • Whitesell L , LindquistSL. HSP90 and the chaperoning of cancer. Nat. Rev. Cancer5(10), 761–72 (2005).
  • Jenke R , ReßingN , HansenFKet al. Anticancer therapy with HDAC inhibitors: mechanism-based combination strategies and future perspectives. Cancers (Basel).13(4), 634 (2021).
  • Linares A , AssouS , LapierreMet al. Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers. Mol. Oncol.13(7), 1534–1547 (2019).
  • Andrikopoulou A , LiontosM , KoutsoukosKet al. The emerging role of BET inhibitors in breast cancer. Breast.53, 152–163 (2020).
  • Munster PN , ThurnKT , ThomasSet al. A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br. J. Cancer.104(12), 1828–35 (2011).
  • Yardley DA , Ismail-KhanRR , MelicharBet al. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J. Clin. Oncol.31(17), 2128–35 (2013).
  • Yeruva SLH , ZhaoF , MillerKDet al. E2112: randomized phase iii trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer. NPJ Breast Cancer4, 1 (2018).
  • Zhou J , WuX , ZhangHet al. Clinical outcomes of tucidinostat-based therapy after prior CDK4/6 inhibitor progression in hormone receptor-positive heavily pretreated metastatic breast cancer. Breast.66, 255–261 (2022).
  • Li X , BaekG , RamanandSGet al. BRD4 promotes DNA repair and mediates the formation of TMPRSS2-ERG gene rearrangements in prostate cancer. Cell Rep.22(3), 796–808 (2018).
  • Choudhry H , HarrisAL. Advances in hypoxia-inducible factor biology. Cell Metab.27(2), 281–298 (2018).
  • Zuco V , DeCesare M , CincinelliRet al. Synergistic antitumor effects of novel HDAC inhibitors and paclitaxel in vitro and in vivo. PLOS ONE6(12), e29085 (2011).
  • Pili R , LiuG , ChintalaSet al. Combination of the histone deacetylase inhibitor vorinostat with bevacizumab in patients with clear-cell renal cell carcinoma: a multicentre, single-arm phase I/II clinical trial. Br. J. Cancer.116(7), 874–883 (2017).
  • Aggarwal R , ThomasS , PawlowskaNet al. Inhibiting histone deacetylase as a means to reverse resistance to angiogenesis inhibitors: phase I study of abexinostat plus pazopanib in advanced solid tumor malignancies. J. Clin. Oncol.35(11), 1231–1239 (2017).
  • Lee S , RauchJ , KolchW. Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity. Int. J. Mol. Sci.21(3), 1102 (2020).
  • Yeon M , KimY , JungHS , JeoungD. Histone deacetylase inhibitors to overcome resistance to targeted and immuno therapy in metastatic melanoma. Front. Cell Dev. Biol.8, 486 (2020).
  • Fallahi-Sichani M , BeckerV , IzarBet al. Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing dedifferentiated state. Mol. Syst. Biol.13(1), 905 (2017).
  • Kitajima S , AsahinaH , ChenTet al. Overcoming resistance to dual innate immune and MEK inhibition downstream of KRAS. Cancer Cell.34(3), 439–452.e6 (2018).
  • Piao J , ChenL , QuanTet al. Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor trichostatin A against NSCLC. Oncotarget.7(37), 60169–60180 (2016).
  • Malone CF , EmersonC , IngrahamRet al. mTOR and HDAC inhibitors converge on the TXNIP/thioredoxin pathway to cause catastrophic oxidative stress and regression of RAS-driven tumors. Cancer Discov.7(12), 1450–1463 (2017).
  • Kumari A , GesumariaL , LiuYJet al. mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer. JCI Insight.8(5), e156657 (2023).
  • Zibelman M , WongYN , DevarajanKet al. Phase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors. Invest. New Drugs.33(5), 1040–7 (2015).
  • Ha K , FiskusW , ChoiDSet al. Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Oncotarget.5(14), 5637–50 (2014).
  • Rasmussen RD , GajjarMK , JensenKE , HamerlikP. Enhanced efficacy of combined HDAC and PARP targeting in glioblastoma. Mol. Oncol.10(5), 751–763 (2016).
  • Konstantinopoulos PA , WilsonAJ , SaskowskiJet al. Suberoylanilide hydroxamic acid (SAHA) enhances olaparib activity by targeting homologous recombination DNA repair in ovarian cancer. Gynecol. Oncol.133(3), 599–606 (2014).
  • Sun C , YinJ , FangYet al. BRD4 inhibition is synthetic lethal with PARP inhibitors through the induction of homologous recombination deficiency. Cancer Cell.33(3), 401–416.e8 (2018).
  • Feng J , MengX. Histone modification and histone modification-targeted anti-cancer drugs in breast cancer: fundamentals and beyond. Front. Pharmacol.13, 946811 (2022)
  • Lau CM , AdamsNM , GearyCDet al. Epigenetic control of innate and adaptive immune memory. Nat. Immunol.19(9), 963–972 (2018).
  • Sharma P , Hu-LieskovanS , WargoJA , RibasA. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell168(4), 707–723 (2017).
  • Topper MJ , VazM , MarroneKAet al. The emerging role of epigenetic therapeutics in immuno-oncology. Nat. Rev. Clin. Oncol.17(2), 75–90 (2020).
  • Sheng W , LaFleurMW , NguyenTHet al. LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell.174(3), 549–563.e19 (2018).
  • Topper MJ , VazM , ChiappinelliKBet al. Epigenetic therapy ties MYC depletion to reversing immune evasion and treating lung cancer. Cell.171(6), 1284–1300.e21 (2017).
  • Goel S , DeCristoMJ , WattACet al. CDK4/6 inhibition triggers anti-tumour immunity. Nature548(7668), 471–475 (2017).
  • Woods DM , SodreAL , VillagraAet al. HDAC inhibition upregulates PD-1 ligands in melanoma and augments immunotherapy with PD-1 blockade. Cancer Immunol. Res.3, 1375–85 (2015)
  • Lisiero DN , SotoH , EversonRGet al. The histone deacetylase inhibitor, LBH589, promotes the systemic cytokine and effector responses of adoptively transferred CD8+ T cells. J. Immunother. Cancer.2, 8 (2014)
  • Degagné E , RomoJ , GallottaMet al. Tumor abscopal responses induced by the TLR9 agonist, SD-101, are strongly potentiated by a HDAC class I inhibitor, domatinostat. [abstract]. Cancer Res.79 (Suppl. 13), 2259 (2019).
  • Goswami S , ApostolouI , ZhangJet al. Modulation of EZH2 expression in T cells improves efficacy of anti-CTLA-4 therapy. J. Clin. Invest.128(9), 3813–3818 (2018).
  • Gounder MM , ZhuG , RoshalLet al. Immunologic correlates of the abscopal effect in a SMARCB1/INI1-negative poorly differentiated chordoma after EZH2 inhibition and radiotherapy. Clin. Cancer Res.25(7), 2064–2071 (2019).
  • Saltos AN , TanvetyanonT , WilliamsCCet al. Phase I/Ib study of pembrolizumab and Vorinostat in patients with metastatic NSCLC (mNSCLC). J. Clin. Oncol.36, 9046–9046 (2018).
  • Khushalani NI , MarkowitzJ , ErogluZet al. A phase I trial of panobinostat with ipilimumab in advanced melanoma. J. Clin. Oncol.35, 9547–9547 (2017).
  • Rodriguez CP , WuQV , VoutsinasJet al. A phase II trial of pembrolizumab and vorinostat in recurrent metastatic head and neck squamous cell carcinomas and salivary gland cancer. Clin. Cancer Res.26(4), 837–845 (2020).
  • Wroblewski M , Scheller-WendorffM , UdontaFet al. BET-inhibition by JQ1 promotes proliferation and self-renewal capacity of hematopoietic stem cells. Haematologica.103(6), 939–948 (2018).
  • Kuang C , ParkY , AugustinRCet al. Pembrolizumab plus azacitidine in patients with chemotherapy refractory metastatic colorectal cancer: a single-arm phase 2 trial and correlative biomarker analysis. Clin. Epigenetics.14(1), 3 (2022).
  • A clinical trial of vorinostat (MK0683, SAHA) in combination with FDA approved cancer drugs in patients with advanced non-small cell lung cancer (NSCLC)(0683–056) – study results - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT00473889 (Accessed: 29th March 2023).
  • Ramalingam SS , MaitlandML , FrankelPet al. Carboplatin and Paclitaxel in combination with either Vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J. Clin. Oncol.28(1), 56–62 (2010).
  • Thomas A , RajanA , SzaboEet al. A phase I/II trial of belinostat in combination with cisplatin, doxorubicin, and cyclophosphamide in thymic epithelial tumors: a clinical and translational study. Clin. Cancer Res.20(21), 5392–402 (2014).
  • Galanis E , AndersonSK , MillerCRet al. Phase I/II trial of Vorinostat combined with temozolomide and radiation therapy for newly diagnosed glioblastoma: results of Alliance N0874/ABTC 02. Neuro Oncol.20(4), 546–556 (2018).
  • Teknos TN , GreculaJ , AgrawalAet al. A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma. Invest New Drugs.37(4), 702–710 (2019).
  • Witta SE , JotteRM , KonduriKet al. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J. Clin. Oncol.30(18), 2248–55 (2012).
  • Gray JE , HauraE , ChiapporiAet al. A phase I, pharmacokinetic, and pharmacodynamic study of panobinostat, an HDAC inhibitor, combined with erlotinib in patients with advanced aerodigestive tract tumors. Clin. Cancer Res.20(6), 1644–55 (2014).
  • Reguart N , RosellR , CardenalFet al. Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression. Lung Cancer.84(2), 161–7 (2014).
  • Ngamphaiboon N , DyGK , MaWWet al. A phase I study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors. Invest. New Drugs.33(1), 225–32 (2015).
  • Sullivan RJ , MoschosSJ , JohnsonMLet al. Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with melanoma previously treated with anti-PD1 therapy[abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019. AACR, Cancer Res.79(Suppl. 13), Abstract nr CT072 (2019).
  • Awad MM , LeBruchec Y , LuBet al. Selective histone deacetylase inhibitor ACY-241 (citarinostat) plus nivolumab in advanced non-small cell lung cancer: results from a phase Ib study. Front. Oncol.11, 696512 (2021).
  • Schwartsmann G , SchunemannH , GoriniCNet al. A phase I trial of cisplatin plus decitabine, a new DNA-hypomethylating agent, in patients with advanced solid tumors and a follow-up early phase II evaluation in patients with inoperable non-small cell lung cancer. Invest. New Drugs.18(1), 83–91 (2000).
  • Tawbi HA , BeumerJH , TarhiniAAet al. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Ann. Oncol.24(4), 1112–9 (2013).
  • Bauman J , VerschraegenC , BelinskySet al. A phase I study of 5-azacytidine and erlotinib in advanced solid tumor malignancies. Cancer Chemother. Pharmacol.69(2), 547–54 (2012).
  • Garrido-Laguna I , McGregorKA , WadeMet al. A phase I/II study of decitabine in combination with panitumumab in patients with wild-type (wt) KRAS metastatic colorectal cancer. Invest. New Drugs.31(5), 1257–64 (2013).
  • Levy BP , GiacconeG , BesseBet al. Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer. Eur. J. Cancer.108, 120–128 (2019).
  • Grossman SR . p300/CBP/p53 interaction and regulation of the p53 response. Eur. J. Biochem.268(10), 2773–8 (2001).
  • Karkhanis V , HuYJ , BaiocchiRAet al. Versatility of PRMT5-induced methylation in growth control and development. Trends Biochem. Sci.36(12), 633–41 (2011).
  • Meng F , LiangZ , ZhaoK , LuoC. Drug design targeting active post-translational modification protein isoforms. Med. Res. Rev.41(3), 1701–1750 (2021).
  • Choy E , FlamandY , BalasubramanianSet al. Phase 1 study of oral abexinostat, a histone deacetylase inhibitor, in combination with doxorubicin in patients with metastatic sarcoma. Cancer.121(8), 1223–30 (2015).
  • Puzanov I , DiabA , AbdallahKet al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J. Immunother. Cancer5(1), 95 (2017).
  • Singh D , KesharwaniP , AlhakamyNA , SiddiqueHR. Accentuating CircRNA-miRNA-transcription factors axis: a conundrum in cancer research. Front. Pharmacol.12, 784801 (2022).
  • Singh D , KhanMA , SiddiqueHR. Role of p53-miRNAs circuitry in immune surveillance and cancer development: a potential avenue for therapeutic intervention. Semin. Cell Dev. Biol.124, 15–25 (2022).
  • Singh D , KhanMA , SiddiqueHR. Specific targeting of cancer stem cells by immunotherapy: a possible stratagem to restrain cancer recurrence and metastasis. Biochem. Pharmacol.198, 114955 (2022).
  • Khan MA , SinghD , AhmadA , SiddiqueHR. Revisiting inorganic nanoparticles as promising therapeutic agents: a paradigm shift in oncological theranostics. Eur. J. Pharm. Sci.164, 105892 (2021).
  • Khan MA , SinghD , ArifAet al. Protective effect of green synthesized selenium nanoparticles against doxorubicin induced multiple adverse effects in Swiss albino mice. Life Sci.305, 120792 (2022).
  • Singh D , KhanMA , SiddiqueHR. PLGA-based nanoparticles for the treatment of inflammatory diseases. In: Micro and Nano Technologies, Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for Drug Delivery.KesherwaniP ( Ed.). Elsevier, 211–233 (2023)
  • Chen F , ShiY , ZhangJ , LiuQ. Nanoparticle-based drug delivery systems for targeted epigenetics cancer therapy. Curr. Drug Targets.21(11), 1084–1098 (2020).

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