A Mini-review on HER2 Positive Breast Cancer and its Metastasis: Resistance and Treatment Strategies

Author(s): Manish Kumar*, P.S. Rajnikanth

Journal Name: Current Nanomedicine
Formerly Recent Patents on Nanomedicine

Volume 10 , Issue 1 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

HER2 positive breast cancer is an aggressive breast cancer followed by brain metastasis, which emerges at the later stage of breast cancer or after a few years of treatment. HER2+ breast cancer brain metastasis is a complex fatal disease with short survival and resistance to first-line drugs such as Trastuzumab, lapatinib, etc. The resistance can be due to the upregulation/downregulation of various proteins of downstream pathways mainly PI3K/AKT pathway and MAPK pathway. In addition, the Blood-brain Barrier (BBB) and Blood Tumor Barrier (BTB) also hinder the delivery to brain metastases. Thus controlling the altered proteins of the downstream pathway can be a targeted approach to control breast cancer and its brain metastasis. At the same time, targeted delivery to metastatic sites can give a synergistic effect in controlling brain metastasis and increasing the survival period. Various type of targeted nanocarriers such as single, dual, or multitargeted, pH specific, or stimuli sensitive nanocarriers can be employed for providing specific delivery to HER2+ cancer cells. Furthermore, combinations such as Trastuzumab with tyrosine kinase inhibitors (lapatinib, neratinib, afatinib), chemotherapeutic drugs (paclitaxel, doxorubicin, capecitabine), or some natural compounds (curcumin, Lycorine, berberine) with anti-apoptotic activity can provide an additional effect in the management of HER2 positive breast cancer and its metastasis.

Keywords: HER2 positive breast cancer, brain metastasis, ERB2 positive breast cancer, trastuzumab, lapatinib, PI3K/AKT pathway, MAPK pathway.

[1]
Liu HT, Ho YS. Anticancer effect of curcumin on breast cancer and stem cells. Food Sci Hum Wellness 2018; 7: 134-7.
[http://dx.doi.org/10.1016/j.fshw.2018.06.001]
[2]
Aebisher D, Bartusik D. Current approaches in breast cancer targeting pharmaceuticals Design of Nano-structures for Theranostics Applications. William Andrew Publishing 2018; pp. 1467-91.
[http://dx.doi.org/10.1016/B978-0-12-813669- 0.00011-7]
[3]
Vogel C, Chan A, Gril B, et al. Management of ErbB2-positive breast cancer: insights from preclinical and clinical studies with lapatinib. Jpn J Clin Oncol 2010; 40(11): 999-1013.
[http://dx.doi.org/10.1093/jjco/hyq084] [PMID: 20542996]
[4]
Chang Y, Park KH, Lee JE, Han KC. Phosphoproteomic analysis reveals PAK2 as a therapeutic target for lapatinib resistance in HER2-positive breast cancer cells. Biochem Biophys Res Commun 2018; 505(1): 187-93.
[http://dx.doi.org/10.1016/j.bbrc.2018.09.086] [PMID: 30243723]
[5]
Kim JY, Cho Y, Oh E, et al. Disulfiram targets cancer stem-like properties and the HER2/Akt signaling pathway in HER2-positive breast cancer. Cancer Lett 2016; 379(1): 39-48.
[http://dx.doi.org/10.1016/j.canlet.2016.05.026] [PMID: 27238567]
[6]
Escrivá-de-Romaní S, Arumí M, Bellet M, Saura C. HER2-positive breast cancer: Current and new therapeutic strategies. Breast 2018; 39: 80-8.
[http://dx.doi.org/10.1016/j.breast.2018.03.006] [PMID: 29631097]
[7]
Wang X, Sun Q, Shen S, Xu Y, Huang L. Nanotrastuzumab in combination with radioimmunotherapy: Can it be a viable treatment option for patients with HER2-positive breast cancer with brain metastasis? Med Hypotheses 2016; 88: 79-81.
[http://dx.doi.org/10.1016/j.mehy.2015.12.014] [PMID: 26880645]
[8]
Petrelli F, Ghidini M, Lonati V, et al. The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis. Eur J Cancer 2017; 84: 141-8.
[http://dx.doi.org/10.1016/j.ejca.2017.07.024] [PMID: 28810186]
[9]
Goyette MA, Duhamel S, Aubert L, et al. The receptor tyrosine kinase AXL is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression. Cell Rep 2018; 23(5): 1476-90.
[http://dx.doi.org/10.1016/j.celrep.2018.04.019] [PMID: 29719259]
[10]
Seoane J, De Mattos-Arruda L. Brain metastasis: new opportunities to tackle therapeutic resistance. Mol Oncol 2014; 8(6): 1120-31.
[http://dx.doi.org/10.1016/j.molonc.2014.05.009] [PMID: 24953014]
[11]
Kabraji S, Ni J, Lin NU, Xie S, Winer EP, Zhao JJ. Drug resistance in HER2-positive breast cancer brain metastases: Blame the barrier or the brain? Clin Cancer Res 2018; 24(8): 1795-804.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3351] [PMID: 29437794]
[12]
Dittmer J. July. Breast cancer stem cells: Features, key drivers and treatment options. Semin Cancer Biol 2018; 53: 59-74.
[13]
Fabi A, Alesini D, Valle E, et al. T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer. Breast 2018; 41: 137-43.
[http://dx.doi.org/10.1016/j.breast.2018.07.004] [PMID: 30092500]
[14]
Yardley DA, Hart LL, Ward PJ, et al. CabazitaxelPlus lapatinib as therapy for HER2+ metastatic breast cancer with intracranial metastases: Results of a dose-finding study. Clin Breast Cancer 2018; 18(5): e781-7.
[http://dx.doi.org/10.1016/j.clbc.2018.03.004]
[15]
Li F, Tang SC. Targeting metastatic breast cancer with ANG1005, a novel peptide-paclitaxel conjugate that crosses the blood-brain-barrier (BBB). Genes Dis 2017; 4: 1-3.
[16]
Hu C, Li M, Guo T, et al. Anti-metastasis activity of curcumin against breast cancer via the inhibition of stem cell-like properties and EMT. Phytomedicine 2019; 58152740
[PMID: 31005718]
[17]
D’Amato V, Raimondo L, Formisano L, et al. Mechanisms of lapatinib resistance in HER2-driven breast cancer. Cancer Treat Rev 2015; 41(10): 877-83.
[http://dx.doi.org/10.1016/j.ctrv.2015.08.001] [PMID: 26276735]
[18]
Amin M, Pourshohod A, Kheirollah A, et al. Specific delivery of idarubicin to HER2-positive breast cancerous cell line by trastuzumab-conjugated liposomes. J Drug Deliv Sci Technol 2018; 47: 209-14.
[http://dx.doi.org/10.1016/j.jddst.2018.07.017]
[19]
Raju A, Muthu MS, Feng SS. Trastuzumab-conjugated vitamin E TPGS liposomes for sustained and targeted delivery of docetaxel. Expert Opin Drug Deliv 2013; 10(6): 747-60.
[http://dx.doi.org/10.1517/17425247.2013.777425] [PMID: 23458409]
[20]
Akhtari J, Rezayat SM, Teymouri M, et al. Targeting, bio distributive and tumor growth inhibiting characterization of anti-HER2 affibody coupling to liposomal doxorubicin using BALB/c mice bearing TUBO tumors. Int J Pharm 2016; 505(1-2): 89-95.
[http://dx.doi.org/10.1016/j.ijpharm.2016.03.060] [PMID: 27039149]
[21]
Zahmatkeshan M, Gheybi F, Rezayat SM, Jaafari MR. Improved drug delivery and therapeutic efficacy of PEgylated liposomal doxorubicin by targeting anti-HER2 peptide in murine breast tumor model. Eur J Pharm Sci 2016; 86: 125-35.
[http://dx.doi.org/10.1016/j.ejps.2016.03.009] [PMID: 26972276]
[22]
Ju RJ, Cheng L, Xiao Y, et al. PTD modified paclitaxel anti-resistant liposomes for treatment of drug-resistant non-small cell lung cancer. J Liposome Res 2018; 28(3): 236-48.
[http://dx.doi.org/10.1080/08982104.2017.1327542] [PMID: 28480778]
[23]
Sonali, Singh RP, Singh N, et al. Transferrin liposomes of docetaxel for brain-targeted cancer applications:formulation and brain theranostics. Drug Deliv 2016; 28(4): 1261-71.
[http://dx.doi.org/10.3109/10717544.2016.1162878] [PMID: 26961144]
[24]
Sonali , Singh RP, Sharma G, et al. RGD-TPGS decorated theranostic liposomes for brain targeted delivery. Colloids Surf B Biointerfaces 2016; 147: 129-41.
[25]
Kumar Mehata A, Bharti S, Singh P, et al. Trastuzumab decorated TPGS-g-chitosan nanoparticles for targeted breast cancer therapy. Colloids Surf B Biointerfaces 2019; 173: 366-77.
[http://dx.doi.org/10.1016/j.colsurfb.2018.10.007] [PMID: 30316083]
[26]
Choi JS, Park JS. Surface modification of docetaxel nanocrystals with HER2 antibody to enhance cell growth inhibition in breast cancer cells. Colloids Surf B Biointerfaces 2017; 159: 139-50.
[http://dx.doi.org/10.1016/j.colsurfb.2017.07.064] [PMID: 28783505]
[27]
Li J, Xu W, Yuan X, et al. Polymer-lipid hybrid anti-HER2 nanoparticles for targeted salinomycin delivery to HER2-positive breast cancer stem cells and cancer cells. Int J Nanomedicine 2017; 12: 6909-21.
[http://dx.doi.org/10.2147/IJN.S144184] [PMID: 29075110]
[28]
Hamilton AM, Aidoudi-Ahmed S, Sharma S, et al. Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental breast cancer metastasis in the brain. J Mol Med (Berl) 2015; 93(9): 991-1001.
[http://dx.doi.org/10.1007/s00109-015-1279-x] [PMID: 25869026]
[29]
Koutsiouki K, Angelopoulou A, Ioannou E, et al. TAT peptide-conjugated magnetic PLA-PEG nano-capsules for the targeted delivery of paclitaxel: In vitro and cell studies. AAPS PharmSciTech 2017; 18(3): 769-81.
[http://dx.doi.org/10.1208/s12249-016-0560-9] [PMID: 27301873]
[30]
Agrawal P, Singh RP, Sonali , et al. TPGS-chitosan cross-linked targeted nanoparticles for effective brain cancer therapy. Mater Sci Eng C 2017; 74: 167-76.
[http://dx.doi.org/10.1016/j.msec.2017.02.008] [PMID: 28254282]
[31]
Ranjbar-Navazi Z, Eskandani M, Johari-Ahar M, et al. Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy. J Drug Target 2018; 26(3): 267-77.
[http://dx.doi.org/10.1080/1061186X.2017.1365876] [PMID: 28795849]
[32]
Ghorbani M, Bigdeli B, Jalili-Baleh L, et al. Curcumin-lipoic acid conjugate as a promising anticancer agent on the surface of gold‑iron oxide nanocomposites: A pH-sensitive targeted drug delivery system for brain cancer theranostics. Eur J Pharm Sci 2018; 114: 175-88.
[http://dx.doi.org/10.1016/j.ejps.2017.12.008] [PMID: 29248558]
[33]
Cheraghi R, Nazari M, Alipour M, Majidi A, Hosseinkhani S. Development of a targeted anti-HER2 scFv chimeric peptide for gene delivery into HER2-positive breast cancer cells. Int J Pharm 2016; 515(1-2): 632-43.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.008] [PMID: 27825868]
[34]
Ding H, Gangalum PR, Galstyan A, et al. HER2-positive breast cancer targeting and treatment by a peptide-conjugated mini nanodrug. Nanomedicine (Lond) 2017; 13(2): 631-9.
[http://dx.doi.org/10.1016/j.nano.2016.07.013] [PMID: 27520726]
[35]
Zhou G, Latchoumanin O, Hebbard L, et al. Aptamers as targeting ligands and therapeutic molecules for overcoming drug resistance in cancers. Adv Drug Deliv Rev 2018; 134: 107-21.
[http://dx.doi.org/10.1016/j.addr.2018.04.005] [PMID: 29627370]
[36]
Cao HH, Chu JH, Kwan HY, et al. Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma. Sci Rep 2016; 6: 21731.
[http://dx.doi.org/10.1038/srep21731] [PMID: 26911838]
[37]
Belfiore L, Saunders DN, Ranson M. et al.Towards clinical translation of ligand-functionalized liposomes in targeted cancer therapy: Challenges and opportunities. J Control Release 2018; 277: 1-13.
[http://dx.doi.org/10.1016/j.jconrel.2018.02.040] [PMID: 29501721]
[38]
Doolittle E, Peiris PM, Doron G, et al. Spatiotemporal targeting of a dual-ligand nanoparticle to cancer metastasis. ACS Nano 2015; 9(8): 8012-21.
[http://dx.doi.org/10.1021/acsnano.5b01552] [PMID: 26203676]
[39]
Tang J, Zhang L, Liu Y, et al. Synergistic targeted delivery of payload into tumor cells by dual-ligand liposomes co-modified with cholesterol anchored transferrin and TAT. Int J Pharm 2013; 454(1): 31-40.
[http://dx.doi.org/10.1016/j.ijpharm.2013.06.048] [PMID: 23850793]
[40]
Ran R, Wang H, Liu Y, et al. Microfluidic self-assembly of a combinatorial library of single- and dual-ligand liposomes for in vitro and in vivo tumor targeting. Eur J Pharm Biopharm 2018; 130: 1-10.
[http://dx.doi.org/10.1016/j.ejpb.2018.06.017] [PMID: 29908938]
[41]
Xu W, Qian J, Hou G, et al. A dual-targeted hyaluronic acid-gold nanorod platform with triple-stimuli responsiveness for photodynamic/photothermal therapy of breast cancer. Acta Biomater 2019; 83: 400-13.
[http://dx.doi.org/10.1016/j.actbio.2018.11.026] [PMID: 30465921]
[42]
Song Y, Tang C, Yin C. Combination antitumor immunotherapy with VEGF and PIGF siRNA via systemic delivery of multi-functionalized nanoparticles to tumor-associated macrophages and breast cancer cells. Biomaterials 2018; 185: 117-32.
[http://dx.doi.org/10.1016/j.biomaterials.2018.09.017] [PMID: 30241030]
[43]
Liu Y, Qiao L, Zhang S, et al. Dual pH-responsive multifunctional nanoparticles for targeted treatment of breast cancer by combining immunotherapy and chemotherapy. Acta Biomater 2018; 66: 310-24.
[http://dx.doi.org/10.1016/j.actbio.2017.11.010] [PMID: 29129789]
[44]
Li M, Shi K, Tang X, et al. Synergistic tumor microenvironment targeting and blood-brain barrier penetration via a pH-responsive dual-ligand strategy for enhanced breast cancer and brain metastasis therapy. Nanomedicine (Lond) 2018; 14(6): 1833-43.
[http://dx.doi.org/10.1016/j.nano.2018.05.008] [PMID: 29800759]
[45]
Cristofolini T, Dalmina M, Sierra JA, et al. Multifunctional hybrid nanoparticles as magnetic delivery systems for siRNA targeting the HER2 gene in breast cancer cells. Mater Sci Eng C 2020; 109110555
[46]
Lakkadwala S, Singh J. Co-delivery of doxorubicin and erlotinib through liposomal nanoparticles for glioblastoma tumor regression using an in vitro brain tumor model. Colloids Surf B Biointerfaces 2019; 173: 27-35.
[http://dx.doi.org/10.1016/j.colsurfb.2018.09.047] [PMID: 30261346]
[47]
Wang R, Yang M, Li G, et al. Paclitaxel-betulinic acid hybrid nanosuspensions for enhanced anti-breast cancer activity. Colloids Surf B Biointerfaces 2019; 174: 270-9.
[http://dx.doi.org/10.1016/j.colsurfb.2018.11.029] [PMID: 30469048]
[48]
Nair JJ, Van Staden J. Caspase-inducing effects of lycorane and crinane alkaloids of the Amaryllidaceae. S Afr J Bot 2019; 120: 33-8.
[http://dx.doi.org/10.1016/j.sajb.2018.05.016]
[49]
Wang C, Wang Q, Li X, et al. Lycorine induces apoptosis of bladder cancer T24 cells by inhibiting phospho-Akt and activating the intrinsic apoptotic cascade. Biochem Biophys Res Commun 2017; 483(1): 197-202.
[http://dx.doi.org/10.1016/j.bbrc.2016.12.168] [PMID: 28042037]
[50]
Wang J, Xu J, Xing G. Lycorine inhibits the growth and metastasis of breast cancer through the blockage of STAT3 signaling pathway. Acta Biochim Biophys Sin (Shanghai) 2017; 49(9): 771-9.
[http://dx.doi.org/10.1093/abbs/gmx076] [PMID: 28910973]
[51]
Ji Y, Yu M, Qi Z, et al. Study on apoptosis effect of human breast cancer cell MCF-7 induced by lycorine hydrochloride via death receptor pathway. Saudi Pharm J 2017; 25(4): 633-7.
[http://dx.doi.org/10.1016/j.jsps.2017.04.036] [PMID: 28579903]
[52]
Liu XS, Jiang J, Jiao XY, Wu YE, Lin JH, Cai YM. Lycorine induces apoptosis and down-regulation of Mcl-1 in human leukemia cells. Cancer Lett 2009; 274(1): 16-24.
[http://dx.doi.org/10.1016/j.canlet.2008.08.029] [PMID: 18829157]
[53]
Jiang QQ, Liu WB. Lycorine inhibits melanoma A375 cell growth and metastasis through the inactivation of the PI3K/AKT signaling pathway. Med Sci 2018; 34: 33-8.
[54]
Cao Z, Yu D, Fu S, et al. Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity. Toxicol Lett 2013; 218(2): 174-85.
[http://dx.doi.org/10.1016/j.toxlet.2013.01.018] [PMID: 23376478]
[55]
Ying X, Huang A, Xing Y, Lan L, Yi Z, He P. Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway. Sci China Life Sci 2017; 60(4): 417-28.
[http://dx.doi.org/10.1007/s11427-016-0368-y] [PMID: 28251459]
[56]
Yuan P, Gao SL. Management of breast cancer brain metastases: Focus on human epidermal growth factor receptor 2-positive breast cancer. Chronic Dis Transl Med 2017; 3(1): 21-32.


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Article Details

VOLUME: 10
ISSUE: 1
Year: 2020
Page: [36 - 47]
Pages: 12
DOI: 10.2174/2468187310666191223141038

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