Resistance and Overcoming Resistance in Breast Cancer

CONCLUSIONS

Cancer is a common disease and represents one of the biggest health problems in the world, with BC being the leading cause of cancer death in women. One of the most significant clinical problems in the treatment of BC is the development of drug resistance. Therefore, the identification of the possible biological and molecular mechanisms involved in such resistance could help the development of new therapeutic targets. Recent research has shown that the application of combined therapies and use of emerging therapies may be effective for overcoming resistance and minimizing side effects, respectively.

Acknowledgments

We thank the Universidad del Rosario for the payment of the edition and publication of the article. The authors also thank Gabrielle White Wolf, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript.

Disclosure

The authors report no conflicts of interest in this work.


Andrea Luque-Bolivar,1 Erika Pérez-Mora,1 Victoria Eugenia Villegas,2 Milena Rondón-Lagos1

1School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia; 2Biology Program, Faculty of Natural Sciences, Universidad del Rosario, Bogotá 111221, Colombia

Correspondence: Victoria Eugenia Villegas
Biology Program, Faculty of Natural Sciences, Universidad del Rosario, Bogotá 111221, Colombia
Tel/Fax +57-1-297-0200 Ext 4029
Email [email protected]
Milena Rondón-Lagos
School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia
Tel/Fax +57-8-7420-8263
Email [email protected]


References

1. International Agency for Research on Cancer. Global cancer observatory. Cancer Today; 2018. Available from: https://gco.iarc.fr/. Accessed November 3, 2020.

2. Waks A, Winer E. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300. doi:10.1001/jama.2018.19323

3. International Agency for Research on Cancer. Global cancer observatory. Latest world cancer statistics – GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence Worldwide in 2012; 2013. Available from: https://www.iarc.fr/news-events/latest-world-cancer-statistics-globocan-2012-estimated-cancer-incidence-mortality-and-prevalence-worldwide-in-2012/. Accessed November 3, 2020.

4. Bray F, Ferlay J, Laversanne M, et al. Cancer I ncidence in F ive C ontinents: inclusion criteria, highlights from Volume X and the global status of cancer registration. Int J Cancer. 2015;137(9):2060–2071. doi:10.1002/ijc.29670

5. Harbeck N, Cortes J, Gnant M, et al. Breast cancer. Nat Rev. 2019;5(66). doi:10.1038/s41572-019-0111-2

6. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68. doi:10.1186/bcr2635

7. Parisot JP, Hu XF, DeLuise M, Zalcberg JR. Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line. Br J Cancer. 1999;79(5–6):693–700. doi:10.1038/sj.bjc.6690112

8. Berry D, Muss H, Thor A, et al. HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor–positive, node-positive breast cancer. J Clin Oncol. 2000;18(20):3471–3479. doi:10.1200/JCO.2000.18.20.3471

9. Tai W, Mahato R, Cheng K. The role of HER2 in cancer therapy and targeted drug delivery. J Control Release. 2010;146(3):264–275. doi:10.1016/j.jconrel.2010.04.009

10. Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–1717. doi:10.1016/S0140-6736(05)66544-0.

11. Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen receptor–positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2016;2(11):1477–1486. doi:10.1001/jamaoncol.2016.1897

12. Rossi V, Berchialla P, Giannarelli D, et al. Should all patients with HR-positive HER2-negative metastatic breast cancer receive CDK 4/6 inhibitor as first-line based therapy? A network meta-analysis of data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT trials. Cancers (Basel). 2019;11(11):1661. doi:10.3390/cancers11111661

13. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–784. doi:10.1016/S0140-6736(11)60993-8.

14. Droog M, Beelen K, Linn S, Zwart W. Tamoxifen resistance: from bench to bedside. Eur J Pharmacol. 2013;717(1–3):47–57. doi:10.1016/j.ejphar.2012.11.071

15. Abe O, Abe R, Enomoto K, et al. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351(9114):1451–1467. doi:10.1016/S0140-6736(97)11423-4

16. Early Breast Cancer Trialists’ Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women.. Lancet. 1992;339(8784):1–15.

17. Colleoni M, Gelber S, Goldhirsch A, et al. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol off J Am Soc Clin Oncol. 2006;24(9):1332–1341. doi:10.1200/JCO.2005.03.0783

18. Kumar R, Zakharov MN, Khan SH, et al. The dynamic structure of the estrogen receptor. J Amino Acids. 2011;2011:1–7. doi:10.4061/2011/812540

19. Kedia-Mokashi N, Makawy AEL, Saxena M, Balasinor NH. Chromosomal aberration in the post-implantation embryos sired by tamoxifen treated male rats. Mutat Res – Genet Toxicol Environ Mutagen. 2010;703(2):169–173. doi:10.1016/j.mrgentox.2010.08.016

20. Bianco S, Gévry N. Endocrine resistance in breast cancer: from cellular signaling pathways to epigenetic mechanisms. Transcription. 2012;3(4):165–170. doi:10.4161/trns.20496

21. Nass N, Kalinski T. Tamoxifen resistance: from cell culture experiments towards novel biomarkers. Pathol Res Pract. 2015;211(3):189–197. doi:10.1016/j.prp.2015.01.004

22. Zundelevich A, Dadiani M, Kahana-Edwin S, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020;22(1):16. doi:10.1186/s13058-020-1246-5

23. Li S, Shen D, Shao J, et al. Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep. 2013;4(6):1116–1130. doi:10.1016/j.celrep.2013.08.022

24. McGraw J, Waller D. Cytochrome P450 variations in different ethnic populations. Expert Opin Drug Metab Toxicol. 2012;8(3):371–382. doi:10.1517/17425255.2012.657626

25. Ignatov A, Ignatov T, Weißenborn C, et al. G-protein-coupled estrogen receptor GPR30 and tamoxifen resistance in breast cancer. Breast Cancer Res Treat. 2011;128(2):457–466. doi:10.1007/s10549-011-1584-1

26. Kang S, Bader A, Vogt P. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A. 2005;102(3):802–807. doi:10.1073/pnas.0408864102

27. Zhao W, Zhang Q, Kang X, Jin S, Lou C. AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells. Biochem Biophys Res Commun. 2009;380(3):699–704. doi:10.1016/j.bbrc.2009.01.155

28. Razavi P, Chang MT, Xu G, et al. The genomic landscape of endocrine-resistant advanced breast cancers. Cancer Cell. 2018;34(3):427–438.e6. doi:10.1016/j.ccell.2018.08.008

29. Huang D, Yang F, Wang Y, Guan X. Mechanisms of resistance to selective estrogen receptor down-regulator in metastatic breast cancer. Biochim Biophys Acta – Rev Cancer. 2017;1868(1):148–156. doi:10.1016/j.bbcan.2017.03.008

30. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275(5308):1943–1947. doi:10.1126/science.275.5308.1943

31. Miller TW, Pérez-Torres M, Narasanna A, et al. Loss of Phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer. Cancer Res. 2009;69(10):4192–4201. doi:10.1158/0008-5472.CAN-09-0042

32. Raha P, Thomas S, Munster PN. Epigenetic modulation: a novel therapeutic target for overcoming hormonal therapy resistance. Epigenomics. 2011;3(4):451–470. doi:10.2217/epi.11.72

33. Noriega-Reyes MY, Langley McCarron E. Estrogen receptor corregulators and their implication in breast cancer. Cancerology. 2008;3:29–40.

34. Huang Y, Jiang D, Sui M, Wang X, Fan W. Fulvestrant reverses doxorubicin resistance in multidrug-resistant breast cell lines independent of estrogen receptor expression. Oncol Rep. 2017;37:705–712. doi:10.3892/or.2016.5315

35. U.S Food and Drug Administration. FDA approves first PI3K inhibitor for breast cancer. Press Announcements; 2019.

36. Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation, and therapeutic targeting. Nat Rev Cancer. 2015;15(1):7–24. doi:10.1038/nrc3860

37. André F, Ciruelos EM, Rubovszky G, et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the Phase 3 SOLAR-1 trial. En: ESMO 2018 CONGRESS. Vol 29; 2018. Available from: https://oncologypro.esmo.org/meeting-resources/esmo-2018-congress/Alpelisib-ALP-fulvestrant-FUL-for-advanced-breast-cancer-ABC-results-of-the-Phase-3-SOLAR-1-trial. Accessed November 3, 2020.

38. Bahrami N, Chang G, Kanaya N, et al. Changes in serum estrogenic activity during neoadjuvant therapy with letrozole and exemestane. J Steroid Biochem Mol Biol. 2020;200:105641. doi:10.1016/j.jsbmb.2020.105641

39. Geisler J, Helle H, Ekse D, et al. Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels. Clin Cancer Res. 2008;14(19):6330–6335. doi:10.1158/1078-0432.CCR-07-5221

40. Carlini P, Michelotti A, Ferretti G, et al. Clinical evaluation of the use of exemestane as further hormonal therapy after nonsteroidal aromatase inhibitors in postmenopausal metastatic breast cancer patients. Cancer Invest. 2007;25(2):102–105. doi:10.1080/07357900701224789

41. Chin YS, Beresford MJ, Ravichandran D, Makris A. Exemestane after non-steroidal aromatase inhibitors for post-menopausal women with advanced breast cancer. Breast. 2007;16(4):436–439. doi:10.1016/j.breast.2007.02.002

42. Sharpless NE, Sherr CJ. Forging a signature of in vivo senescence. Nat Rev Cancer. 2015;15(7):397–408. doi:10.1038/nrc3960

43. Spring LM, Wander SA, Zangardi M, Bardia A. CDK 4/6 inhibitors in breast cancer: current controversies and future directions. Curr Oncol Rep. 2019;21(3):25. doi:10.1007/s11912-019-0769-3

44. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638–3646. doi:10.1200/JCO.2017.75.6155

45. Sledge GW, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875–2884. doi:10.1200/JCO.2017.73.7585

46. Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2− metastatic breast cancer. Clin Cancer Res. 2017;23(17):5218–5224. doi:10.1158/1078-0432.CCR-17-0754

47. Chong QY, Kok ZH, Bui NLC, et al. A unique CDK4/6 inhibitor: current and future therapeutic strategies of abemaciclib. Pharmacol Res. 2020;156:104686. doi:10.1016/j.phrs.2020.104686

48. Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised Phase 2 study. Lancet Oncol. 2015;16(1):25–35. doi:10.1016/S1470-2045(14)71159-3

49. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–1748. doi:10.1056/NEJMoa1609709

50. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018;379(20):1926–1936. doi:10.1056/NEJMoa1810527

51. Killock D. CDK4/6 inhibitors prolong OS. Nat Rev Clin Oncol. 2019;1.

52. Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov. 2015;14(2):130–146. doi:10.1038/nrd4504

53. Miller TW, Hennessy BT, González-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor–positive human breast cancer. J Clin Invest. 2010;120(7):2406–2413. doi:10.1172/JCI41680

54. Verret B, Cortes J, Bachelot T, Andre F, Arnedos M. Efficacy of PI3K inhibitors in advanced breast cancer. Ann Oncol. 2019;30(Supplement_10):x12–x20. doi:10.1093/annonc/mdz381

55. Ma CX, Luo J, Naughton M, et al. A Phase I trial of BKM120 (Buparlisib) in combination with fulvestrant in postmenopausal women with estrogen receptor–positive metastatic breast cancer. Clin Cancer Res. 2016;22(7):1583–1591. doi:10.1158/1078-0432.CCR-15-1745

56. Krop IE, Mayer IA, Ganju V, et al. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016;17(6):811–821. doi:10.1016/S1470-2045(16)00106-6

57. Hurvitz SA, Peddi PF. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. Breast Dis. 2013;24(1):79–81. doi:10.1016/j.breastdis.2013.01.007

58. Dhakal A, Antony Thomas R, Levine EG, et al. Outcome of everolimus-based therapy in hormone-receptor-positive metastatic breast cancer patients after progression on palbociclib. Breast Cancer Basic Clin Res. 2020;14:1178223420944864. doi:10.1177/1178223420944864

59. Langedijk J, Mantel-Teeuwisse AK, Slijkerman DS, Schutjens M-HDB. Drug repositioning and repurposing: terminology and definitions in literature. Drug Discov Today. 2015;20(8):1027–1034. doi:10.1016/j.drudis.2015.05.001

60. D’Amelio P, Isaia GC. The use of raloxifene in osteoporosis treatment. Expert Opin Pharmacother. 2013;14(7):949–956. doi:10.1517/14656566.2013.782002

61. Waters EA, McNeel TS, Stevens WM, Freedman AN. Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010. Breast Cancer Res Treat. 2012;134(2):875–880. doi:10.1007/s10549-012-2089-2

62. Lippman ME, Cummings SR, Disch DP, et al. Effect of raloxifene on the incidence of invasive breast cancer in postmenopausal women with osteoporosis categorized by breast cancer risk. Clin Cancer Res. 2006;12(17):5242–5247. doi:10.1158/1078-0432.CCR-06-0688

63. Shah RR, Stonier PD. Repurposing old drugs in oncology: opportunities with clinical and regulatory challenges ahead. J Clin Pharm Ther. 2019;44(1):6–22.

64. Denslow A, Świtalska M, Jarosz J, et al. Clopidogrel in a combined therapy with anticancer drugs—effect on tumor growth, metastasis, and treatment toxicity: studies in animal models. PLoS One. 2017;12(12):e0188740. doi:10.1371/journal.pone.0188740

65. White C, Alshaker H, Cooper C, Winkler M, Pchejetski D. The emerging role of FTY720 (Fingolimod) in cancer treatment. Oncotarget. 2016;7(17):23106. doi:10.18632/oncotarget.7145

66. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP, Vikas P. The repurposing drugs in oncology (ReDO) project. Ecancermedicalscience. 2014;8. doi:10.3332/ecancer.2014.485

67. Barok M, Isola J, Pályi-Krekk Z, et al. Trastuzumab causes antibody-dependent cellular cytotoxicity–mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance. Mol Cancer Ther. 2007;6(7):2065–2072. doi:10.1158/1535-7163.MCT-06-0766

68. Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med. 2000;6(4):443–446. doi:10.1038/74704

69. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing drugs in oncology (ReDO) – mebendazole as an anti-cancer agent. Ecancermedicalscience. 2014;8(1). doi:10.3332/ecancer.2014.443

70. Nagata Y, Lan K, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6(2):117–127. doi:10.1016/j.ccr.2004.06.022

71. Moasser M. Targeting the function of the HER2 oncogene in human cancer therapeutics. Oncogene. 2007;26(46):6577–6592. doi:10.1038/sj.onc.1210478

72. Shi Y, Fan X, Meng W, Deng H, Zhang N, An Z. Engagement of immune effector cells by trastuzumab induces HER2/ERBB2 downregulation in cancer cells through STAT1 activation. Breast Cancer Res. 2014;16(2):R33. doi:10.1186/bcr3637

73. Scaltriti M, Rojo F, Ocaña A, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007;99(8):628–638. doi:10.1093/jnci/djk134

74. Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006;3(5):269–280. doi:10.1038/ncponc0509

75. Nagy P, Friedländer E, Tanner M, et al. Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res. 2005;65(2):473–482.

76. Campbell I, Russell S, Choong D, et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res. 2004;64(21):7678–7681. doi:10.1158/0008-5472.CAN-04-2933

77. Warmerdam P, Van de Winkel J, Vlug A, Westerdaal N, Capel P. A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding. J Immunol. 1991;147(4):1338–1343.

78. Christianson T, Doherty J, Lin Y, et al. NH2-terminally truncated HER-2/neu protein: relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res. 1998;58(22):5123–5129.

79. U.S. Food and Drug Administration. FDA approves first PI3K inhibitor for breast cancer. FDA news release; 2019. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-pi3k-inhibitor-breast-cancer. Accessed November 3, 2020.

80. Quandt D, Fiedler E, Boettcher D, Marsch WC, Seliger B. B7-h4 expression in human melanoma: its association with patients’ survival and antitumor immune response. Clin Cancer Res. 2011;17(10):3100–3111.

81. Swain SM, Baselga J, Kim S-B, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–734. doi:10.1056/NEJMoa1413513

82. Ishii K, Morii N, Yamashiro H. Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy. Core Evid. 2019;14:51–70. doi:10.2147/ce.s217848

83. Zhang X, Chen J, Weng Z, et al. A new anti-HER2 antibody that enhances the anti-tumor efficacy of trastuzumab and pertuzumab with a distinct mechanism of action. Mol Immunol. 2020;119:48–58. doi:10.1016/j.molimm.2020.01.009

84. Qin H, Liu L, Sun S, et al. The impact of PI3K inhibitors on breast cancer cell and its tumor microenvironment. PeerJ. 2018;6:e5092. doi:10.7717/peerj.5092

85. Tran B, Bedard PL. Luminal-B breast cancer and novel therapeutic targets. Breast Cancer Res. 2011;13(6):221. doi:10.1186/bcr2904

86. Tong CWS, Wu M, Cho W, To KKW. Recent advances in the treatment of breast cancer. Front Oncol. 2018;8:227. doi:10.3389/fonc.2018.00227

87. Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res. 2014;16(2):1–12. doi:10.1186/bcr3621

88. Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382(7):610–621. doi:10.1056/NEJMoa1914510

89. Begovac M QTc prolongation in patients treated with trastuzumab and ado-trastuzumab-emtazine; 2019. Available from: https://repozitorij.mef.unizg.hr/islandora/object/mef:2463. Accessed November 3, 2020.

90. Hunter FW, Barker HR, Lipert B, et al. Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. Br J Cancer. 2019;122(5):603–612. doi:10.1158/1535-7163.MCT-17-0296

91. Modi S, Tsurutani J, Tamura K, et al. Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-low expressing breast cancer: updated results of a large phase 1 study. Cancer Res. 2019;79(4Suppl):P6–17.

92. Skidmore L, Sakamuri S, Knudsen N, et al. ARX788, a site-specific anti-HER2 antibody drug conjugate, demonstrates potent and selective activity in HER2 low and T-DM1 resistant breast and gastric cancers. Mol Cancer Ther. 2020:molcanther.1004.2019. doi:10.1158/1535-7163.MCT-19-1004.

93. Newman DJ, Cragg GM. Current status of marine-derived compounds as warheads in anti-tumor drug candidates. Mar Drugs. 2017;15(4):99. doi:10.3390/md15040099

94. Barok M, Le Joncour V, Martins A, et al. ARX788, a novel anti-HER2 antibody-drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer. Cancer Lett. 2020;473:156–163. doi:10.1016/j.canlet.2019.12.037

95. Rinnerthaler G, Gampenrieder SP, Greil R. HER2 directed antibody-drug-conjugates beyond T-DM1 in breast cancer. Int J Mol Sci. 2019;20(5):1115. doi:10.3390/ijms20051115

96. Yurkovetskiy A, Gumerov D, Ter-Ovanesyan E, et al. Non-clinical pharmacokinetics of XMT-1522, a HER2 targeting auristatin-based antibody drug conjugate. Cancer Res. 2017;77(13):48. doi:10.1158/1538-7445.AM2017-48

97. Bergstrom DA, Bodyak N, Park PU, et al. Abstract P4-14-28: XMT-1522 induces tumor regressions in pre-clinical models representing HER2-positive and HER2 low-expressing breast cancer. 2016. doi:10.1158/1538-7445.SABCS15-P4-14-28

98. Traore T, Khattar M. Abstract lb-294: synergy of an anti-HER2 ADC TAK-522 (XMT-1522) in combination with anti-PD1 monoclonal antibody (MAB) in a syngeneic breast cancer model expressing human HER2. 2018. doi:10.1158/1538-7445.AM2018-LB-294

99. Murphy CG, Modi S. HER2 breast cancer therapies: a review. Biol Targets Ther. 2009;3:289–301. doi:10.2147/BTT.S3479

100. Rabindran SK, Discafani CM, Rosfjord EC, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004;64(11):3958–3965. doi:10.1158/0008-5472.CAN-03-2868

101. Li M, Hirano K, Ikeda Y, et al. Triglyceride deposit cardiomyovasculopathy: a rare cardiovascular disorder. Orphanet J Rare Dis. 2019;14(1):1–9. doi:10.1186/s13023-019-1087-4

102. Moulder SL, Borges VF, Baetz T, et al. Phase I study of ONT-380, a HER2 inhibitor, in patients with HER2+-advanced solid tumors, with an expansion cohort in HER2+ metastatic breast cancer (MBC). Clin Cancer Res. 2017;23(14):3529–3536. doi:10.1158/1078-0432.CCR-16-1496

103. Murthy R, Borges VF, Conlin A, et al. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19(7):880–888. doi:10.1016/S1470-2045(18)30256-0

104. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597–609. doi:10.1056/NEJMoa1914609

105. Bonnefoi H, Grellety T, Tredan O, et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016;27(5):812–818. doi:10.1093/annonc/mdw067

106. Subramanian S, Prasanna R, Biswas G, et al. Nanosomal docetaxel lipid suspension-based chemotherapy in breast cancer: results from a multicenter retrospective study. Breast Cancer Targets Ther. 2020;12:77–85. doi:10.2147/BCTT.S236108

107. Loibl S, Furlanetto J. Targeting the immune system in breast cancer: hype or hope?: TILs and newer immune-based therapies being evaluated for HER2+ and TNBC. Curr Breast Cancer Rep. 2015;7(4):203–209. doi:10.1007/s12609-015-0193-0

108. Verweij J, Clavel M, Chevalier B. Paclitaxel (TaxolTM) and docetaxel (TaxotereTM): not simply two of a kind. Ann Oncol. 1994;5(6):495–505. doi:10.1093/oxfordjournals.annonc.a058903

109. Norouzi S, Gorgi Valokala M, Mosaffa F, Zirak MR, Zamani P, Behravan J. Crosstalk in cancer resistance and metastasis. Crit Rev Oncol Hematol. 2018;132:145–153. doi:10.1016/j.critrevonc.2018.09.017

110. Ponnusamy L, Mahalingaiah PKS, Chang YW, Singh KP. Reversal of epigenetic aberrations associated with the acquisition of doxorubicin resistance restores drug sensitivity in breast cancer cells. Eur J Pharm Sci. 2018;123:56–69. doi:10.1016/j.ejps.2018.07.028

111. Tang Y, Wang Y, Kiani MF, Wang B. Classification, treatment strategy, and associated drug resistance in breast cancer. Clin Breast Cancer. 2016;16(5):335–343. doi:10.1016/j.clbc.2016.05.012

112. Yu D, Wu Y, Shen H, et al. Exosomes in development, metastasis and drug resistance of breast cancer. Cancer Sci. 2015;106(8):959–964. doi:10.1111/cas.12715

113. Ji X, Lu Y, Tian H, Meng X, Wei M, Cho WC. Chemoresistance mechanisms of breast cancer and their countermeasures. Biomed Pharmacother. 2019;114:108800. doi:10.1016/j.biopha.2019.108800

114. Jing X, Zhang H, Hu J, et al. β-arrestin 2 is associated with multidrug resistance in breast cancer cells through regulating MDR1 gene expression. Int J Clin Exp Pathol. 2015;8(2):1354–1363.

115. Gao X, Wu Y, Qiao L, Feng X. SENP2 suppresses NF-κB activation and sensitizes breast cancer cells to doxorubicin. Eur J Pharmacol. 2019;854:179–186. doi:10.1016/j.ejphar.2019.03.051

116. Dueñas-Gonzalez A, Coronel J, Cetina L, González-Fierro A, Chavez-Blanco A, Taja-Chayeb L. Hydralazine-valproate: a repositioned drug combination for the epigenetic therapy of cancer. Expert Opin Drug Metab Toxicol. 2014;10(10):1433–1444. doi:10.1517/17425255.2014.947263

117. Tan C, Hu W, He Y, et al. Cytokine-mediated therapeutic resistance in breast cancer. Cytokine. 2018;108:151–159. doi:10.1016/j.cyto.2018.03.020

118. DeMichele A, Yee D, Esserman L. Mechanisms of resistance to neoadjuvant chemotherapy in breast cancer. N Engl J Med. 2017;377(23):2287–2289. doi:10.1056/NEJMcibr1711545

119. Tsuruo T, Naito M, Tomida A, et al. Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci. 2003;94(1):15–21. doi:10.1111/j.1349-7006.2003.tb01345.x

120. Hasim MS, Nessim C, Villeneuve PJ, Vanderhyden BC, Dimitroulakos J. Activating transcription factor 3 as a novel regulator of chemotherapy response in breast cancer. Transl Oncol. 2018;11(4):988–998. doi:10.1016/j.tranon.2018.06.001

121. Davis T, van Niekerk G, Peres J, Prince S, Loos B, Engelbrecht AM. Doxorubicin resistance in breast cancer: a novel role for the human protein AHNAK. Biochem Pharmacol. 2018;148:174–183. doi:10.1016/j.bcp.2018.01.012

122. Crown J. A review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer. Semin Oncol. 1999;26(1supl. 3):5–9.

123. Jazieh K, Bell R, Agarwal N, Abraham J. Novel targeted therapies for metastatic breast cancer. Ann Transl Med. 2020;8(14):907. doi:10.21037/atm.2020.03.43

124. Ghaderi F, Ahmadvand S, Ramezani A, Montazer M, Ghaderi A. Production and characterization of monoclonal antibody against a triple negative breast cancer cell line. Biochem Biophys Res Commun. 2018;505(1):181–186. doi:10.1016/j.bbrc.2018.09.087

125. Maruthanila VL, Elancheran R, Kunnumakkara AB, Kabilan S, Kotoky J. Recent development of targeted approaches for the treatment of breast cancer. Breast Cancer. 2017;24(2):191–219. doi:10.1007/s12282-016-0732-1

126. Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 2019;20(3):e175–e186. doi:10.1016/S1470-2045(19)30026-9

127. Le Du F, Perrin C, Brunot A, et al. Therapeutic innovations in breast cancer. Presse Med. 2019;48(10):1131–1137. doi:10.1016/j.lpm.2019.04.005

128. Miklavčič D, Mali B, Kos B, Heller R, Serša G. Electrochemotherapy: from the drawing board into medical practice. Biomed Eng Online. 2014;13(1):1–20. doi:10.1186/1475-925X-13-29

129. Mittal L, Aryal UK, Camarillo IG, Raman V, Sundararajan R. Effective electrochemotherapy with curcumin in MDA-MB-231-human, triple negative breast cancer cells: a global proteomics study. Bioelectrochemistry. 2020;131:107350. doi:10.1016/j.bioelechem.2019.107350

130. Mittal L, Raman V, Camarillo IG, Garner AL, Sundararajan R. Viability and cell cycle studies of metastatic triple negative breast cancer cells using low voltage electrical pulses and herbal curcumin. Biomed Phys Eng Express. 2019;5(2):25040. doi:10.1088/2057-1976/aaf2c3

131. Mittal L, Camarillo IG, Varadarajan GS, Srinivasan H, Aryal UK, Sundararajan R. High-throughput, label-free quantitative proteomic studies of the anticancer effects of electrical pulses with turmeric silver nanoparticles: an in vitro model study. Sci Rep. 2020;10(1):1–18. doi:10.1038/s41598-020-64128-8

132. Ahmad A, Sheikh S, Taran R, et al. Therapeutic efficacy of a novel nanosomal docetaxel lipid suspension compared with taxotere in locally advanced or metastatic breast cancer patients. Clin Breast Cancer. 2014;14(3):177–181. doi:10.1016/j.clbc.2013.09.011

133. Moses C, Garcia-Bloj B, Harvey AR, Blancafort P. Hallmarks of cancer: the CRISPR generation. Eur J Cancer. 2018;93:10–18. doi:10.1016/j.ejca.2018.01.002

134. Wang H, Sun W. CRISPR-mediated targeting of HER2 inhibits cell proliferation through a dominant negative mutation. Cancer Lett. 2017;385:137–143. doi:10.1016/j.canlet.2016.10.033

135. Liu B, Saber A, Haisma HJ. CRISPR/Cas9: a powerful tool for identification of new targets for cancer treatment. Drug Discov Today. 2019;24(4):955–970. doi:10.1016/j.drudis.2019.02.011

136. Yi L, Li J. CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges. Biochim Biophys Acta Rev Cancer. 2016;1866(2):197–207. doi:10.1016/j.bbcan.2016.09.002

137. Mughees M, Kumar K, Wajid S. Exosome vesicle as a nano-therapeutic carrier for breast cancer. J Drug Target. 2020;8:1–28. doi:10.1080/1061186X.2020.1808001

138. Yong T, Zhang X, Bie N, et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat Commun. 2019;10(1). doi:10.1038/s41467-019-11718-4

139. Nassar FJ, Nasr R, Talhouk R. MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction. Pharmacol Ther. 2017;172:34–49. doi:10.1016/j.pharmthera.2016.11.012

140. Çalışkan M, Güler H, Bozok Çetintaş V. Current updates on microRNAs as regulators of chemoresistance. Biomed Pharmacother. 2017;95:1000–1012. doi:10.1016/j.biopha.2017.08.084

141. Tomar D, Yadava AS, Kumar D, Bhadauriya G, Kundu GC. Non-coding RNAs as potential therapeutic targets in breast cancer. Biochim Biophys Acta Gene Regul Mech. 2019;863(4):194. doi:10.1016/j.bbagrm.2019.04.005

142. Houssen ME, Ghazy HF, Farag K, et al. Serum atrial natriuretic peptide: a suspected biomarker of breast cancer. Contemp Oncol. 2017;21(1):54. doi:10.5114/wo.2017.66657

143. Aleck K, Hallman K, Quigley M, et al. Effects of atrial natriuretic peptide on p53 and estrogen receptor in breast cancer cells. BioResearch. 2017;6(1):141–150. doi:10.1089/biores.2017.0009

144. Van Nuffel AMT, Sukhatme V, Pantziarka P, Meheus L, Sukhatme VP, Bouche G. Repurposing drugs in oncology (ReDO) – clarithromycin as an anti-cancer agent. Ecancermedicalscience. 2015;9:1–26. doi:10.3332/ecancer.2015.513

145. Griffin F, Marignol L. Therapeutic potential of melatonin for breast cancer radiation therapy patients. Int J Radiat Biol. 2018;94(5):472–477. doi:10.1080/09553002.2018.1446227

146. Amaral MEA, Nery LR, Leite CE, de Azevedo WF, Campos MM. Pre-clinical effects of metformin and aspirin on the cell lines of different breast cancer subtypes. Invest New Drugs. 2018;36(5):782–796. doi:10.1007/s10637-018-0568-y

147. Sharma N, Thomas S, Golden EB, et al. Inhibition of autophagy and induction of breast cancer cell death by mefloquine, an antimalarial agent. Cancer Lett. 2012;326(2):143–154. doi:10.1016/j.canlet.2012.07.029

148. Lamb R, Ozsvari B, Lisanti CL, et al. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget. 2015;6(7):4569. doi:10.18632/oncotarget.3174

149. Ishida J, Konishi M, Ebner N, Springer J. Repurposing of approved cardiovascular drugs. J Transl Med. 2016;14(1):269. doi:10.1186/s12967-016-1031-5

150. Graça I, Sousa EJ, Costa-Pinheiro P, et al. Anti-neoplastic properties of hydralazine in prostate cancer. Oncotarget. 2014;5(15):5950–5964. doi:10.18632/oncotarget.1909

151. Liu B, Huang X, Hu Y, et al. Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer. Oncotarget. 2016;7(36):58038. doi:10.18632/oncotarget.10846

152. Niu G, Liao Z, Cai L, Wei R, Sun L. The combined effects of celecoxib and minocycline hydrochloride on inhibiting the osseous metastasis of breast cancer in nude mice. Cancer Biother Radiopharm. 2008;23(4):469–476. doi:10.1089/cbr.2008.0475

153. Hu J, Ljubimova JY, Inoue S, et al. Phosphodiesterase type 5 inhibitors increase Herceptin transport and treatment efficacy in mouse metastatic brain tumor models. PLoS One. 2010;5(4):e10108. doi:10.1371/journal.pone.0010108

154. Pantziarka P, Bryan BA, Crispino S, Dickerson EB. Propranolol and breast cancer—a work in progress. Ecancermedicalscience. 2018;12:1–6. doi:10.3332/ecancer.2018.ed82

155. Chamaraux-Tran TN, Mathelin C, Aprahamian M, et al. Antitumor effects of lidocaine on human breast cancer cells: an in vitro and in vivo experimental trial. Anticancer Res. 2018;38(1):95–105. doi:10.21873/anticanres.12196

156. Park S-H, Chung YM, Ma J, Yang Q, Berek JS, Hu MCT. Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo. Oncotarget. 2016;7(27):42110. doi:10.18632/oncotarget.9881

157. Chen C-T, Chen Y-C, Yamaguchi H, Hung M-C. Carglumic acid promotes apoptosis and suppresses cancer cell proliferation in vitro and in vivo. Am J Cancer Res. 2015;5(12):3560.

158. Tury S, Assayag F, Bonin F, et al. The iron chelator deferasirox synergises with chemotherapy to treat triple‐negative breast cancers. J Pathol. 2018;246(1):103–114. doi:10.1002/path.5104

159. Goh W, Sleptsova-Freidrich I, Petrovic N. Use of proton pump inhibitors as adjunct treatment for triple-negative breast cancers. An introductory study. J Pharm Pharm Sci. 2014;17(3):439–446. doi:10.18433/j34608

160. Greenshields AL, Fernando W, Hoskin DW. The anti-malarial drug artesunate causes cell cycle arrest and apoptosis of triple-negative MDA-MB-468 and HER2-enriched SK-BR-3 breast cancer cells. Exp Mol Pathol. 2019;107:10–22. doi:10.1016/j.yexmp.2019.01.006

161. Talarico G, Orecchioni S, Dallaglio K, et al. Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells. Sci Rep. 2016;6:18673. doi:10.1038/srep18673

162. Zhang L, Wang X, Chen P. MiR-204 down regulates SIRT1 and reverts SIRT1-induced epithelial-mesenchymal transition, anoikis resistance and invasion in gastric cancer cells. BMC Cancer. 2013;13:1–9. doi:10.1186/1471-2407-13-290

163. Zeng H, Wang L, Wang J, et al. microRNA-129-5p suppresses Adriamycin resistance in breast cancer by targeting SOX2. Arch Biochem Biophys. 2018;651:52–60. doi:10.1016/j.abb.2018.05.018

164. Cochrane D, Spoelstra N, Howe E, Nordeen S, Richer J. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther. 2009;8(5):1055–1066. doi:10.1158/1535-7163.MCT-08-1046

165. Bian X, Liang Z, Feng A, Salgado E, Shim H. HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL. Biochem Pharmacol. 2018;147:30–37. doi:10.1016/j.bcp.2017.11.008

166. Han B, Huang J, Han Y, et al. The microRNA miR-181c enhances chemosensitivity and reduces chemoresistance in breast cancer cells via down-regulating osteopontin. Int J Biol Macromol. 2019;125:544–556. doi:10.1016/j.ijbiomac.2018.12.075

167. Gao L, Guo Q, Li X, et al. MiR-873/PD-L1 axis regulates the stemness of breast cancer cells. EBioMedicine. 2019;41:395–407. doi:10.1016/j.ebiom.2019.02.034

168. Setijono SR, Park M, Kim O, Kim Y, Won Cho K, Jung Song S. miR-218 and miR-129 regulate breast cancer progression by targeting Lamins. Biochem Biophys Res Commun. 2018;496(3):826–833. doi:10.1016/j.bbrc.2018.01.146

169. Muluhngwi P, Klinge CM. Identification of miRNAs as biomarkers for acquired endocrine resistance in breast cancer. Mol Cell Endocrinol. 2017;456:76–86. doi:10.1016/j.mce.2017.02.004

170. Kagepura Thammaiah C, Jayaram S. Role of let-7 family microRNA in breast cancer. Non-Coding RNA Res. 2016;1(1):77–82. doi:10.1016/j.ncrna.2016.10.003

171. Li B, Lu Y, Yu L, et al. miR-221/222 promote cancer stem-like cell properties and tumor growth of breast cancer via targeting PTEN and sustained Akt/NF-κB/COX-2 activation. Chem Biol Interact. 2017;277:33–42. doi:10.1016/j.cbi.2017.08.014

172. Eissa S, Matboli M, Sharawy A, El-Sharkawi F. Prognostic and biological significance of microRNA-221 in breast cancer. Gene. 2015;574(1):163–167. doi:10.1016/j.gene.2015.08.004

173. Geng W, Song H, Zhao Q, et al. MiR-520h stimulates drug resistance to paclitaxel by targeting the OTUD3-PTEN axis in breast cancer. Biomed Res Int. 2020;2020:1–11. doi:10.1155/2020/9512793

Source: Breast Cancer: Targets and Therapy.
Originally published November 11, 2020.

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