Advances in HER2-Targeted Treatment for Advanced/Metastatic Urothelial Carcinoma
Main Article Content
Keywords
摘要
Urothelial carcinoma (UC) represents a common malignancy of the urinary system that can involve the kidneys, ureter, bladder, and urethra. Advanced/metastatic UC (mUC) tends to have a poor prognosis. UC ranks third in terms of human epidermal growth factor receptor 2 (HER2) overexpression among all tumors. However, multiple studies found that, unlike breast cancer, variable degrees of HER2 positivity and poor consistency between HER2 protein overexpression and gene amplification have been found. Trials involving trastuzumab, pertuzumab, lapatinib, afatinib, and neratinib have failed to prove their beneficial effect in patients with HER2-positive mUC, and a clinical trial on T-DM1 (trastuzumab emtansine) was terminated prematurely because of the adverse reactions. However, a phase II trial showed that RC48-ADC was effective. In this review, we provided an in-depth overview of the advances in the research regarding HER2-targeted therapy and the role of HER2 in mUC. Furthermore, we also discussed the prospects of potential strategies aimed at overcoming anti-HER2 resistance, and summarize the novel anti-HER2 approaches for the management of mUC used in recent clinical trials.
##plugins.generic.paperbuzz.metrics##
参考
2. Mollica V, Rizzo A, Montironi R, Cheng L, Giunchi F, Schiavina R, et al. Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma. Cancers (Basel). 2020;12(6). Epub 2020/06/06. https://doi.org/10.3390/cancers12061449.. PubMed PMID: 32498352; PubMed Central PMCID: PMCPMC7352972.
3. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul;23(21):4602–8.
4. Park I, Lee JL. Systemic treatment for advanced urothelial cancer: an update on recent clinical trials and current treatment options. Korean J Intern Med. 2020;35(4):834-53. Epub 2020/07/16. https://doi.org/10.3904/kjim.2020.204.. PubMed PMID: 32668516; PubMed Central PMCID: PMCPMC7373963.
5. Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cell. 2017;171(3):540-56 e25. Epub 2017/10/11. https://doi.org/10.1016/j.cell.2017.09.007.. PubMed PMID: 28988769; PubMed Central PMCID: PMCPMC5687509.
6. Oh DY, Bang YJ. HER2-targeted therapies - a role beyond breast cancer. Nat Rev Clin Oncol. 2020 Jan;17(1):33–48.
7. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009 Apr;14(4):320–68.
8. Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021 Jun;18(6):327–44.
9. Hansel DE, Swain E, Dreicer R, Tubbs RR. HER2 overexpression and amplification in urothelial carcinoma of the bladder is associated with MYC coamplification in a subset of cases. Am J Clin Pathol. 2008 Aug;130(2):274–81.
10. Appert-Collin A, Hubert P, Cremel G, Bennasroune A. Role of ErbB Receptors in Cancer Cell Migration and Invasion. Front Pharmacol. 2015;6:283. Epub 2015/12/05. https://doi.org/10.3389/fphar.2015.00283.. PubMed PMID: 26635612; PubMed Central PMCID: PMCPMC4657385.
11. Roskoski R Jr. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacol Res. 2014 Jan;79:34–74.
12. Kovacs E, Zorn JA, Huang Y, Barros T, Kuriyan J. A structural perspective on the regulation of the epidermal growth factor receptor. Annu Rev Biochem. 2015;84(1):739–64.
13. Jimenez RE, Hussain M, Bianco Jr FJ, Vaishampayan U, Tabazcka P, Sakr WA, et al. Her-2/neu Overexpression in Muscle-invasive Urothelial Carcinoma of the Bladder: Prognostic Significance and Comparative Analysis in Primary and Metastatic Tumors. clinical cancer research. 2001;7(8):2440-7.
14. Diamantis N, Banerji U. Antibody-drug conjugates--an emerging class of cancer treatment. Br J Cancer. 2016;114(4):362-7. Epub 2016/01/08. https://doi.org/10.1038/bjc.2015.435.. PubMed PMID: 26742008; PubMed Central PMCID: PMCPMC4815767.
15. Ravi P, McGregor BA. Antibody-drug conjugates for the treatment of urothelial carcinoma. Expert Opin Biol Ther. 2021 Jul;21(7):915–22.
16. Herter-Sprie GS, Greulich H, Wong KK. Activating Mutations in ERBB2 and Their Impact on Diagnostics and Treatment. Front Oncol. 2013 Apr;3:86.
17. Bai X, He W, Yin H, Li X, Zhou X, Wei Z, et al. Prognostic significance of HER2 status evaluation using immunohistochemistry in patients with urothelial carcinoma of the bladder: A retrospective single center experience. Exp Ther Med. 2022 Oct;24(5):704.
18. Kiss B, Wyatt AW, Douglas J, Skuginna V, Mo F, Anderson S, et al. Her2 alterations in muscle-invasive bladder cancer: Patient selection beyond protein expression for targeted therapy. Sci Rep. 2017;7:42713. Epub 2017/02/17. https://doi.org/10.1038/srep42713.. PubMed PMID: 28205537; PubMed Central PMCID: PMCPMC5311866.
19. Nedjadi T, Al-Maghrabi J, Assidi M, Dallol A, Al-Kattabi H, Chaudhary A, et al. Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques. BMC Cancer. 2016 Aug;16(1):653.
20. Olsson H, Fyhr IM, Hultman P, Jahnson S. HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder. Scand J Urol Nephrol. 2012 Apr;46(2):102–7.
21. Fleischmann A, Rotzer D, Seiler R, Studer UE, Thalmann GN. Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol. 2011 Aug;60(2):350–7.
22. Agrawal V, Bharti N, Pandey R. Human epidermal growth factor receptor 2 (HER2) gene amplification in non-muscle invasive urothelial bladder cancers: Identification of patients for targeted therapy. Arab J Urol. 2020;18(4):267-72. Epub 2020/12/15. https://doi.org/10.1080/2090598X.2020.1814183.. PubMed PMID: 33312739; PubMed Central PMCID: PMCPMC7717524.
23. Hayashi T, Seiler R, Oo HZ, Jäger W, Moskalev I, Awrey S, et al. Targeting HER2 with T-DM1, an Antibody Cytotoxic Drug Conjugate, is Effective in HER2 Over Expressing Bladder Cancer. J Urol. 2015 Oct;194(4):1120–31.
24. Chen PC, Yu HJ, Chang YH, Pan CC. Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression. J Clin Pathol. 2013 Feb;66(2):113–9.
25. Tsai YS, Tzai TS, Chow NH. Does HER2 immunoreactivity provide prognostic information in locally advanced urothelial carcinoma patients receiving adjuvant M-VEC chemotherapy? Urol Int. 2007;79(3):210–6.
26. Matsubara H, Yamada Y, Naruse K, Nakamura K, Aoki S, Taki T, et al. Potential for HER-2/neu molecular targeted therapy for invasive bladder carcinoma: comparative study of immunohistochemistry and fluorescent in situ hybridization. Oncol Rep. 2008 Jan;19(1):57–63.
27. Drago JZ, Ferraro E, Abuhadra N, Modi S. Beyond HER2: targeting the ErbB receptor family in breast cancer. Cancer Treat Rev. 2022 Sep;109:102436.
28. Mishra R, Hanker AB, Garrett JT. Genomic alterations of ERBB receptors in cancer: clinical implications. Oncotarget. 2017 Nov;8(69):114371–92.
29. Sarfaty M, Rosenberg JE. Antibody-Drug Conjugates in Urothelial Carcinomas. Curr Oncol Rep. 2020 Feb;22(2):13.
30. Lae M, Couturier J, Oudard S, Radvanyi F, Beuzeboc P, Vieillefond A. Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients. Ann Oncol. 2010;21(4):815-9. Epub 2009/11/06. https://doi.org/10.1093/annonc/mdp488.. PubMed PMID: 19889613; PubMed Central PMCID: PMCPMC2844947.
31. Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, et al. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 2013 Feb;3(2):224–37.
32. Arribas J, Baselga J, Pedersen K, Parra-Palau JL. p95HER2 and breast cancer. Cancer Res. 2011 Mar;71(5):1515–9.
33. Luque-Cabal M, Garcia-Teijido P, Fernandez-Perez Y, Sanchez-Lorenzo L, Palacio-Vazquez I. Mechanisms Behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer and Strategies to Overcome It. Clin Med Insights Oncol. 2016;10(Suppl 1):21-30. Epub 2016/04/05. https://doi.org/10.4137/CMO.S34537.. PubMed PMID: 27042153; PubMed Central PMCID: PMCPMC4811269.
34. Nagano M, Kohsaka S, Ueno T, Kojima S, Saka K, Iwase H, et al. High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2. Clin Cancer Res. 2018 Oct;24(20):5112–22.
35. Saeki H, Oki E, Kashiwada T, Arigami T, Makiyama A, Iwatsuki M, et al.; Kyushu Study Group of Clinical Cancer (KSCC). Re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab (KSCC1604). Eur J Cancer. 2018 Dec;105:41–9.
36. Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018;554(7691):189-94. Epub 2018/02/09. https://doi.org/10.1038/nature25475.. PubMed PMID: 29420467; PubMed Central PMCID: PMCPMC5808581.
37. Ross JS, Wang K, Al-Rohil RN, Nazeer T, Sheehan CE, Otto GA, et al. Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy. Mod Pathol. 2014 Feb;27(2):271–80.
38. Madison RW, Gupta SV, Elamin YY, Lin DI, Pal SK, Necchi A, et al. Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions. BJU Int. 2020 May;125(5):739–46.
39. de Martino M, Zhuang D, Klatte T, Rieken M, Roupret M, Xylinas E, et al. Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib. Cancer Biol Ther. 2014;15(9):1239-47. Epub 2014/06/28. https://doi.org/10.4161/cbt.29687.. PubMed PMID: 24971884; PubMed Central PMCID: PMCPMC4128866.
40. Wülfing C, Machiels JP, Richel DJ, Grimm MO, Treiber U, De Groot MR, et al. A single-arm, multicenter, open-label phase 2 study of lapatinib as the second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma. Cancer. 2009 Jul;115(13):2881–90.
41. Cerbone L, Sternberg CN, Sengeløv L, Agerbaek M, Van Herpen C, Marreaud S, et al. Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer: EORTC Trial 30061. Oncology. 2016;90(1):21–8.
42. Powles T, Huddart RA, Elliott T, Sarker SJ, Ackerman C, Jones R, et al. Phase III, Double-Blind, Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2-Positive Metastatic Bladder Cancer. J Clin Oncol. 2017 Jan;35(1):48–55.
43. Chen D, Ye Y, Guo S, Yao K. Progress in the Research and Targeted Therapy of ErbB/HER Receptors in Urothelial Bladder Cancer. Front Mol Biosci. 2021 Dec;8:800945.
44. Tang S, Dorff TB, Tsao-Wei DD, Massopust K, Ketchens C, Hu J, et al. Single arm phase II study of docetaxel and lapatinib in metastatic urothelial cancer: USC trial 4B-10-4. American Society of Clinical Oncology; 2016.
45. Galsky MD, Von Hoff DD, Neubauer M, Anderson T, Fleming M, Nagarwala Y, et al. Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. Invest New Drugs. 2012 Apr;30(2):695–701.
46. Kancha RK, von Bubnoff N, Bartosch N, Peschel C, Engh RA, Duyster J. Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib. PLoS One. 2011;6(10):e26760. Epub 2011/11/03. https://doi.org/10.1371/journal.pone.0026760.. PubMed PMID: 22046346; PubMed Central PMCID: PMCPMC3203921.
47. Maeda S, Sakai K, Kaji K, Iio A, Nakazawa M, Motegi T, et al. Lapatinib as first-line treatment for muscle-invasive urothelial carcinoma in dogs. Sci Rep. 2022 Jan;12(1):4.
48. Choudhury NJ, Campanile A, Antic T, Yap KL, Fitzpatrick CA, Wade JL, 3rd, et al. Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in Patients With ERBB Alterations. J Clin Oncol. 2016;34(18):2165-71. Epub 2016/04/06. https://doi.org/10.1200/JCO.2015.66.3047.. PubMed PMID: 27044931; PubMed Central PMCID: PMCPMC5569685.
49. Kwak EL, Shapiro GI, Cohen SM, Becerra CR, Lenz HJ, Cheng WF, et al. Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. Cancer. 2013 Aug;119(16):3043–51.
50. Kong A, Feldinger K. Profile of neratinib and its potential in the treatment of breast cancer. Breast Cancer: Targets and Therapy. 2015. . https://doi.org/10.2147/BCTT.S54414.
51. Grivas PD, Day KC, Karatsinides A, Paul A, Shakir N, Owainati I, et al. Evaluation of the antitumor activity of dacomitinib in models of human bladder cancer. Mol Med. 2013;19:367-76. Epub 2013/10/30. https://doi.org/10.2119/molmed.2013.00108.. PubMed PMID: 24166682; PubMed Central PMCID: PMCPMC3883970.
52. Li X, Yang C, Wan H, Zhang G, Feng J, Zhang L, et al. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Dec;110:51–61.
53. Li S, Liu Q, Liu M, Liu T. Response to Pyrotinib in a Patient with Metastatic Bladder Urothelial Carcinoma Harboring HER2 V842I Mutation: A Case Report. Cancer Manag Res. 2022 Sep;14:2927–32.
54. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009 May;15(5):429–40.
55. Oudard S, Culine S, Vano Y, Goldwasser F, Théodore C, Nguyen T, et al. Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Eur J Cancer. 2015 Jan;51(1):45–54.
56. Hussain MH, MacVicar GR, Petrylak DP, Dunn RL, Vaishampayan U, Lara PN Jr, et al.; National Cancer Institute. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol. 2007 Jun;25(16):2218–24.
57. Michaelson MD, Hu C, Pham HT, Dahl DM, Lee-Wu C, Swanson GP, et al. A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524). Int J Radiat Oncol Biol Phys. 2017;97(5):995-1001. Epub 2017/03/24. https://doi.org/10.1016/j.ijrobp.2016.12.018.. PubMed PMID: 28333021; PubMed Central PMCID: PMCPMC5536836.
58. Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, et al. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. J Clin Oncol. 2018 Feb;36(6):536–42.
59. Sweeney CJ, Hainsworth JD, Bose R, Burris HA, Kurzrock R, Swanton C, et al. MyPathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment of a Tissue-Agnostic Cohort of Patients With Human Epidermal Growth Factor Receptor 2-Altered Advanced Solid Tumors. J Clin Oncol. 2023 Oct;•••:JCO2202636. https://doi.org/10.1200/JCO.22.02636.
60. Tarantino P, Carmagnani Pestana R, Corti C, Modi S, Bardia A, Tolaney SM, et al. Antibody-drug conjugates: smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 2022 Mar;72(2):165–82.
61. Li BT, Makker V, Buonocore DJ, Offin MD, Olah ZT, Panora E, et al. A multi-histology basket trial of ado-trastuzumab emtansine in patients with HER2 amplified cancers. Journal of Clinical Oncology. 2018;36(15_suppl):2502-. https://doi.org/10.1200/JCO.2018.36.15_suppl.2502..
62. Xu Y, Wang Y, Gong J, Zhang X, Peng Z, Sheng X, et al. Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors. Gastric Cancer. 2021 Jul;24(4):913–25.
63. Sheng X, Wang L, He Z, Shi Y, Luo H, Han W, et al. Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials. J Clin Oncol. 2023 Nov;•••:JCO2202912. https://doi.org/10.1200/JCO.22.02912.
64. Sheng X, Zhou L, Yang K, Zhang S, Xu H, Yan X, et al. Disitamab vedotin, a novel humanized anti-HER2 antibody-drug conjugate (ADC), combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma: An open-label phase 1b/2 study. Journal of Clinical Oncology. 2023;41(16_suppl):4566-. https://doi.org/10.1200/JCO.2023.41.16_suppl.4566..
65. Xu H, Sheng X, Zhou L, Yan X, Li S, Chi Z, et al. A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. Journal of Clinical Oncology. 2022;40(16_suppl):4519-. https://doi.org/10.1200/JCO.2022.40.16_suppl.4519..
66. Meric-Bernstam F, Johnson AM, Dumbrava EEI, Raghav K, Balaji K, Bhatt M, et al. Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer. Clin Cancer Res. 2019;25(7):2033-41. Epub 2018/11/18. https://doi.org/10.1158/1078-0432.CCR-18-2275.. PubMed PMID: 30442682; PubMed Central PMCID: PMCPMC6445731.
67. Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-Targeting Antibody-Drug Conjugate, Trastuzumab Deruxtecan (DS-8201a), Enhances Antitumor Immunity in a Mouse Model. Mol Cancer Ther. 2018 Jul;17(7):1494–503.
68. Galsky MD, Conte GD, Foti S, Yu EY, Machiels J-PH, Doger B, et al. Primary analysis from DS8201-A-U105: A phase 1b, two-part, open-label study of trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing urothelial carcinoma (UC). Journal of Clinical Oncology. 2022;40(6_suppl):438-. https://doi.org/10.1200/JCO.2022.40.6_suppl.438..
69. Meric-Bernstam F, Makker V, Oaknin A, Oh DY, Banerjee S, González-Martín A, et al. Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial. J Clin Oncol. 2023 Oct;•••:JCO2302005. https://doi.org/10.1200/JCO.23.02005.
70. Banerji U, van Herpen CM, Saura C, Thistlethwaite F, Lord S, Moreno V, et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Aug;20(8):1124–35.
71. Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, et al. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017 Apr;28(4):855–61.
72. Moyes K, Brender T, Smith SW, Xu H, Setter B, Fan L-Q, et al. Abstract 3271: A systemically administered, conditionally active TLR8 agonist for the treatment of HER2-expressing tumors. Cancer Research. 2019;79(13_Supplement):3271-. https://doi.org/10.1158/1538-7445.AM2019-3271. %J Cancer Research.
73. Bajorin DF, Sharma P, Quinn DI, Plimack ER, Hoffman-Censits JH, O'Donnell PH, et al. Phase 2 trial results of DN24-02, a HER2-targeted autologous cellular immunotherapy in HER2+ urothelial cancer patients (pts). Journal of Clinical Oncology. 2016;34(15_suppl):4513-. https://doi.org/10.1200/JCO.2016.34.15_suppl.4513..
74. Boni V, Sharma MR, Patnaik A. The Resurgence of Antibody Drug Conjugates in Cancer Therapeutics: Novel Targets and Payloads. Am Soc Clin Oncol Educ Book. 2020 Mar;40(40):1–17.
75. Hamblett K, Barnscher S, Davies R, Hammond P, Hernandez A, Wickman G, et al. Abstract P6-17-13: ZW49, a HER2 targeted biparatopic antibody drug conjugate for the treatment of HER2 expressing cancers. Cancer Research. 2019;79(4_Supplement):P6-17-3-P6--3. https://doi.org/10.1158/1538-7445.SABCS18-P6-17-13. %J Cancer Research.
76. Sheng X, Yan X, Wang L, Shi Y, Yao X, Luo H, et al. Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma. Clin Cancer Res. 2021 Jan;27(1):43–51.
77. Scaltriti M, Rojo F, Ocaña A, Anido J, Guzman M, Cortes J, 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 Apr;99(8):628–38.
78. Sperinde J, Jin X, Banerjee J, Penuel E, Saha A, Diedrich G, et al. Quantitation of p95HER2 in paraffin sections by using a p95-specific antibody and correlation with outcome in a cohort of trastuzumab-treated breast cancer patients. Clin Cancer Res. 2010 Aug;16(16):4226–35.
79. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004 Aug;6(2):117–27.
80. Gewinner C, Wang ZC, Richardson A, Teruya-Feldstein J, Etemadmoghadam D, Bowtell D, et al. Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell. 2009 Aug;16(2):115–25.
81. Gallardo A, Lerma E, Escuin D, Tibau A, Munoz J, Ojeda B, et al. Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. Br J Cancer. 2012;106(8):1367-73. Epub 2012/03/29. https://doi.org/10.1038/bjc.2012.85.. PubMed PMID: 22454081; PubMed Central PMCID: PMCPMC3326683.
82. Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol. 2008 Apr;26(11):1789–96.