The application and progress of antibody-drug conjugate in advanced gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Ziyao , MA Jichun , ZHU Chenglou ,  DA Mingxu

The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding author：

DA Mingxu, Email: hxdamingxu@hotmail.com

Keywords：

gastric cancer; antibody-drug conjugate; mechanism; therapy

DOI：

10.7507/1007-9424.202307004

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective This study aims to summarize the application and research progress of antibody-drug conjugates (ADC) in gastric cancer (GC). Method We reviewed recent domestic and international research on ADC in GC and conducted a comprehensive summary. Results ADC was emerging as one of the most effective therapeutic options for advanced GC patients, significantly impacting the treatment and prognosis of these patients. However, their clinical application had certain limitations in some aspects. There were some kinds of ADC targeting human epidermal growth factor receptor-2, human epidermal growth factor receptor-3, guanylyl cyclase C, and trophoblasti surface antigen 2. Furthermore, the development of ADC with multiple mechanisms of action held great promise. Conclusion ADC drugs represent a valuable approach for the treatment of GC and offer new perspectives and insights into the management of GC patients.

Citation： WU Ziyao, MA Jichun, ZHU Chenglou, DA Mingxu. The application and progress of antibody-drug conjugate in advanced gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(11): 1372-1377. doi: 10.7507/1007-9424.202307004 Copy

1.	Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric Cancer, Version 2. 2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2022, 20(2): 167-192.
2.	Li K, Zhang A, Li X, et al. Advances in clinical immunotherapy for gastric cancer. Biochim Biophys Acta Rev Cancer, 2021, 1876(2): 188615. doi: 10.1016/j.bbcan.2021.188615.
3.	Ponte JF, Lanieri L, Khera E, et al. Antibody co-administration can improve systemic and local distribution of antibody-drug conjugates to increase in vivo efficacy. Mol Cancer Ther, 2021, 20(1): 203-212.
4.	Dean AQ, Luo S, Twomey JD, et al. Targeting cancer with antibody-drug conjugates: promises and challenges. MAbs, 2021, 13(1): 1951427. doi: 10.1080/19420862.2021.1951427.
5.	Ornes S. Antibody-drug conjugates. Proc Natl Acad Sci U S A, 2013, 110(34): 13695. doi: 10.1073/pnas.1314120110.
6.	Swaminathan M, Cortes JE. Update on the role of gemtuzumab-ozogamicin in the treatment of acute myeloid leukemia. Ther Adv Hematol, 2023, 14: 20406207231154708.
7.	Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol, 2019, 20(6): 816-826.
8.	Bang K, Cheon J, Park YS, et al. Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab. Gastric Cancer, 2022, 25(4): 794-803.
9.	Steffenfauseweh H, Rottschäfer D, Vishnevskiy YV, et al. Isolation of an annulated 1, 4-distibabenzene diradicaloid. Angew Chem Int Ed Engl, 2023, 62(19): e202216003. doi: 10.1002/anie.202216003.
10.	Schwartz RS. Paul Ehrlich’s magic bullets. N Engl J Med, 2004, 350(11): 1079-1080.
11.	Jin Y, Edalatian Zakeri S, Bahal R, et al. New technologies bloom together for bettering cancer drug conjugates. Pharmacol Rev, 2022, 74(3): 680-711.
12.	Nagornov KO, Gasilova N, Kozhinov AN, et al. Drug-to-antibody ratio estimation via proteoform peak integration in the analysis of antibody-oligonucleotide conjugates with orbitrap fourier transform mass spectrometry. Anal Chem, 2021, 93(38): 12930-12937.
13.	Wolska-Washer A, Robak T. Safety and tolerability of antibody-drug conjugates in cancer. Drug Saf, 2019, 42(2): 295-314.
14.	Groff D, Carlos NA, Chen R, et al. Development of an E. coli strain for cell-free ADC manufacturing. Biotechnol Bioeng, 2022, 119(1): 162-175.
15.	Yu J, Song Y, Tian W. How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J Hematol Oncol, 2020, 13(1): 45. doi: 10.1186/s13045-020-00876-4.
16.	Sawant MS, Streu CN, Wu L, et al. Toward drug-like multispecific antibodies by design. Int J Mol Sci, 2020, 21(20): 7496.
17.	Kang TH, Jung ST. Boosting therapeutic potency of antibodies by taming Fc domain functions. Exp Mol Med, 2019, 51(11): 1-9.
18.	Li Z, Li Y, Chang HP, et al. Effect of size on solid tumor disposition of protein therapeutics. Drug Metab Dispos, 2019, 47(10): 1136-1145.
19.	MacTaggart B, Kashina A. Posttranslational modifications of the cytoskeleton. Cytoskeleton (Hoboken), 2021, 78(4): 142-173.
20.	Hong Y, Nam SM, Moon A. Antibody-drug conjugates and bispecific antibodies targeting cancers: applications of click chemistry. Arch Pharm Res, 2023, 46(3): 131-148.
21.	Jin Y, Schladetsch MA, Huang X, et al. Stepping forward in antibody-drug conjugate development. Pharmacol Ther, 2022, 229: 107917. doi: 10.1016/j.pharmthera.2021.107917.
22.	Conilh L, Sadilkova L, Viricel W, et al. Payload diversification: a key step in the development of antibody-drug conjugates. J Hematol Oncol, 2023, 16(1): 3. doi: 10.1186/s13045-022-01397-y.
23.	Li F, Emmerton KK, Jonas M, et al. Intracellular released payload influences potency and bystander-killing effects of antibody-drug conjugates in preclinical models. Cancer Res, 2016, 76(9): 2710-2719.
24.	Su Z, Xiao D, Xie F, et al. Antibody-drug conjugates: recent advances in linker chemistry. Acta Pharm Sin B, 2021, 11(12): 3889-3907.
25.	Hååg P, Olsson M, Forsberg J, et al. Caspase-2 is a mediator of apoptotic signaling in response to gemtuzumab ozogamicin in acute myeloid leukemia. Cell Death Discov, 2022, 8(1): 284. doi: 10.1038/s41420-022-01071-9.
26.	Yang X, Li C, Li P, et al. Ratiometric optical probes for biosensing. Theranostics, 2023, 13(8): 2632-2656.
27.	Giugliano F, Corti C, Tarantino P, et al. Bystander effect of antibody-drug conjugates: fact or fiction? Curr Oncol Rep, 2022, 24(7): 809-817.
28.	Modi S, Park H, Murthy RK, et al. Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low-expressing advanced breast cancer: results from a phase Ⅰb study. J Clin Oncol, 2020, 38(17): 1887-1896.
29.	Ogitani Y, Hagihara K, Oitate M, et al. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci, 2016, 107(7): 1039-1046.
30.	Yamashita-Kashima Y, Shu S, Osada M, et al. Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation. Cancer Chemother Pharmacol, 2020, 86(5): 641-654.
31.	Loganzo F, Tan X, Sung M, et al. Tumor cells chronically treated with a trastuzumab-maytansinoid antibody-drug conjugate develop varied resistance mechanisms but respond to alternate treatments. Mol Cancer Ther, 2015, 14(4): 952-963.
32.	Le Joncour V, Martins A, Puhka M, et al. A novel anti-HER2 antibody-drug conjugate XMT-1522 for HER2-positive breast and gastric cancers resistant to trastuzumab emtansine. Mol Cancer Ther, 2019, 18(10): 1721-1730.
33.	叶春, 祁兴顺, 李谦谦, 等. XELOX联合曲妥珠单抗在HER2阳性老年晚期胃癌转化治疗中的疗效观察. 中国普外基础与临床杂志, 2022, 29(12): 1623-1627.
34.	Tarantino P, Tolaney SM. The dawn of the antibody-drug conjugates era: how T-DM1 reinvented the future of chemotherapy for solid tumors. Cancer Res, 2022, 82(20): 3659-3661.
35.	Barok M, Tanner M, Köninki K, et al. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett, 2011, 306(2): 171-179.
36.	Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med, 2012, 367(19): 1783-1791.
37.	Oh DY, Bang YJ. HER2-targeted therapies - a role beyond breast cancer. Nat Rev Clin Oncol, 2020, 17(1): 33-48.
38.	Thuss-Patience PC, Shah MA, Ohtsu A, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol, 2017, 18(5): 640-653.
39.	Seo S, Ryu MH, Park YS, et al. Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3). Gastric Cancer, 2019, 22(3): 527-535.
40.	Deeks ED. Disitamab vedotin: first approval. Drugs, 2021, 81(16): 1929-1935.
41.	Xu Y, Wang Y, Gong J, 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, 24(4): 913-925.
42.	Peng Z, Liu T, Wei J, et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase Ⅱ study. Cancer Commun (Lond), 2021, 41(11): 1173-1182.
43.	Takegawa N, Nonagase Y, Yonesaka K, et al. DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase Ⅰ inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance. Int J Cancer, 2017, 141(8): 1682-1689.
44.	Shitara K, Iwata H, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol, 2019, 20(6): 827-836.
45.	Zhang J, Ji D, Shen W, et al. Phase Ⅰ trial of a novel anti-HER2 antibody-drug conjugate, ARX788, for the treatment of HER2-positive metastatic breast cancer. Clin Cancer Res, 2022: OF1-OF10.
46.	Skidmore L, Sakamuri S, Knudsen NA, 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, 19(9): 1833-1843.
47.	Zhang Y, Qiu MZ, Wang JF, et al. Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma. Cell Rep Med, 2022, 3(11): 100814. doi: 10.1016/ j.xcrm.2022.100814.
48.	Capone E, Lattanzio R, Gasparri F, et al. EV20/NMS-P945, a novel thienoindole based antibody-drug conjugate targeting HER-3 for solid tumors. Pharmaceutics, 2021, 13(4): 483. doi: 10.3390/pharmaceutics13040483.
49.	Prasad H, Mathew JKK, Visweswariah SS. Receptor guanylyl cyclase C and cyclic GMP in health and disease: perspectives and therapeutic opportunities. Front Endocrinol (Lausanne), 2022, 13: 911459. doi: 10.3389/fendo.2022.911459.
50.	Almhanna K, Kalebic T, Cruz C, et al. Phase Ⅰ study of the investigational anti-guanylyl cyclase antibody-drug conjugate TAK-264 (MLN0264) in adult patients with advanced gastrointestinal malignancies. Clin Cancer Res, 2016, 22(20): 5049-5057.
51.	Bang YJ, Takano T, Lin CC, et al. TAK-264 (MLN0264) in previously treated Asian patients with advanced gastrointestinal carcinoma expressing guanylyl cyclase C: results from an open-label, non-randomized phase 1 study. Cancer Res Treat, 2018, 50(2): 398-404.
52.	Qiu S, Zhang J, Wang Z, et al. Targeting Trop-2 in cancer: recent research progress and clinical application. Biochim Biophys Acta Rev Cancer, 2023, 1878(4): 188902. doi: 10.1016/ j.bbcan.2023.188902.
53.	Cardillo TM, Govindan SV, Sharkey RM, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2/SN-38 antibody-drug conjugate: characterization and efficacy in pancreatic, gastric, and other cancers. Bioconjug Chem, 2015, 26(5): 919-931.
54.	Cheng Y, Yuan X, Tian Q, et al. Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front Oncol, 2022, 12: 951589. doi: 10.3389/fonc.2022.951589.
55.	Fuentes-Antrás J, Genta S, Vijenthira A, et al. Antibody-drug conjugates: in search of partners of choice. Trends Cancer, 2023, 9(4): 339-354.

1. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric Cancer, Version 2. 2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2022, 20(2): 167-192.
2. Li K, Zhang A, Li X, et al. Advances in clinical immunotherapy for gastric cancer. Biochim Biophys Acta Rev Cancer, 2021, 1876(2): 188615. doi: 10.1016/j.bbcan.2021.188615.
3. Ponte JF, Lanieri L, Khera E, et al. Antibody co-administration can improve systemic and local distribution of antibody-drug conjugates to increase in vivo efficacy. Mol Cancer Ther, 2021, 20(1): 203-212.
4. Dean AQ, Luo S, Twomey JD, et al. Targeting cancer with antibody-drug conjugates: promises and challenges. MAbs, 2021, 13(1): 1951427. doi: 10.1080/19420862.2021.1951427.
5. Ornes S. Antibody-drug conjugates. Proc Natl Acad Sci U S A, 2013, 110(34): 13695. doi: 10.1073/pnas.1314120110.
6. Swaminathan M, Cortes JE. Update on the role of gemtuzumab-ozogamicin in the treatment of acute myeloid leukemia. Ther Adv Hematol, 2023, 14: 20406207231154708.
7. Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol, 2019, 20(6): 816-826.
8. Bang K, Cheon J, Park YS, et al. Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab. Gastric Cancer, 2022, 25(4): 794-803.
9. Steffenfauseweh H, Rottschäfer D, Vishnevskiy YV, et al. Isolation of an annulated 1, 4-distibabenzene diradicaloid. Angew Chem Int Ed Engl, 2023, 62(19): e202216003. doi: 10.1002/anie.202216003.
10. Schwartz RS. Paul Ehrlich’s magic bullets. N Engl J Med, 2004, 350(11): 1079-1080.
11. Jin Y, Edalatian Zakeri S, Bahal R, et al. New technologies bloom together for bettering cancer drug conjugates. Pharmacol Rev, 2022, 74(3): 680-711.
12. Nagornov KO, Gasilova N, Kozhinov AN, et al. Drug-to-antibody ratio estimation via proteoform peak integration in the analysis of antibody-oligonucleotide conjugates with orbitrap fourier transform mass spectrometry. Anal Chem, 2021, 93(38): 12930-12937.
13. Wolska-Washer A, Robak T. Safety and tolerability of antibody-drug conjugates in cancer. Drug Saf, 2019, 42(2): 295-314.
14. Groff D, Carlos NA, Chen R, et al. Development of an E. coli strain for cell-free ADC manufacturing. Biotechnol Bioeng, 2022, 119(1): 162-175.
15. Yu J, Song Y, Tian W. How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J Hematol Oncol, 2020, 13(1): 45. doi: 10.1186/s13045-020-00876-4.
16. Sawant MS, Streu CN, Wu L, et al. Toward drug-like multispecific antibodies by design. Int J Mol Sci, 2020, 21(20): 7496.
17. Kang TH, Jung ST. Boosting therapeutic potency of antibodies by taming Fc domain functions. Exp Mol Med, 2019, 51(11): 1-9.
18. Li Z, Li Y, Chang HP, et al. Effect of size on solid tumor disposition of protein therapeutics. Drug Metab Dispos, 2019, 47(10): 1136-1145.
19. MacTaggart B, Kashina A. Posttranslational modifications of the cytoskeleton. Cytoskeleton (Hoboken), 2021, 78(4): 142-173.
20. Hong Y, Nam SM, Moon A. Antibody-drug conjugates and bispecific antibodies targeting cancers: applications of click chemistry. Arch Pharm Res, 2023, 46(3): 131-148.
21. Jin Y, Schladetsch MA, Huang X, et al. Stepping forward in antibody-drug conjugate development. Pharmacol Ther, 2022, 229: 107917. doi: 10.1016/j.pharmthera.2021.107917.
22. Conilh L, Sadilkova L, Viricel W, et al. Payload diversification: a key step in the development of antibody-drug conjugates. J Hematol Oncol, 2023, 16(1): 3. doi: 10.1186/s13045-022-01397-y.
23. Li F, Emmerton KK, Jonas M, et al. Intracellular released payload influences potency and bystander-killing effects of antibody-drug conjugates in preclinical models. Cancer Res, 2016, 76(9): 2710-2719.
24. Su Z, Xiao D, Xie F, et al. Antibody-drug conjugates: recent advances in linker chemistry. Acta Pharm Sin B, 2021, 11(12): 3889-3907.
25. Hååg P, Olsson M, Forsberg J, et al. Caspase-2 is a mediator of apoptotic signaling in response to gemtuzumab ozogamicin in acute myeloid leukemia. Cell Death Discov, 2022, 8(1): 284. doi: 10.1038/s41420-022-01071-9.
26. Yang X, Li C, Li P, et al. Ratiometric optical probes for biosensing. Theranostics, 2023, 13(8): 2632-2656.
27. Giugliano F, Corti C, Tarantino P, et al. Bystander effect of antibody-drug conjugates: fact or fiction? Curr Oncol Rep, 2022, 24(7): 809-817.
28. Modi S, Park H, Murthy RK, et al. Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low-expressing advanced breast cancer: results from a phase Ⅰb study. J Clin Oncol, 2020, 38(17): 1887-1896.
29. Ogitani Y, Hagihara K, Oitate M, et al. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci, 2016, 107(7): 1039-1046.
30. Yamashita-Kashima Y, Shu S, Osada M, et al. Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation. Cancer Chemother Pharmacol, 2020, 86(5): 641-654.
31. Loganzo F, Tan X, Sung M, et al. Tumor cells chronically treated with a trastuzumab-maytansinoid antibody-drug conjugate develop varied resistance mechanisms but respond to alternate treatments. Mol Cancer Ther, 2015, 14(4): 952-963.
32. Le Joncour V, Martins A, Puhka M, et al. A novel anti-HER2 antibody-drug conjugate XMT-1522 for HER2-positive breast and gastric cancers resistant to trastuzumab emtansine. Mol Cancer Ther, 2019, 18(10): 1721-1730.
33. 叶春, 祁兴顺, 李谦谦, 等. XELOX联合曲妥珠单抗在HER2阳性老年晚期胃癌转化治疗中的疗效观察. 中国普外基础与临床杂志, 2022, 29(12): 1623-1627.
34. Tarantino P, Tolaney SM. The dawn of the antibody-drug conjugates era: how T-DM1 reinvented the future of chemotherapy for solid tumors. Cancer Res, 2022, 82(20): 3659-3661.
35. Barok M, Tanner M, Köninki K, et al. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett, 2011, 306(2): 171-179.
36. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med, 2012, 367(19): 1783-1791.
37. Oh DY, Bang YJ. HER2-targeted therapies - a role beyond breast cancer. Nat Rev Clin Oncol, 2020, 17(1): 33-48.
38. Thuss-Patience PC, Shah MA, Ohtsu A, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol, 2017, 18(5): 640-653.
39. Seo S, Ryu MH, Park YS, et al. Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3). Gastric Cancer, 2019, 22(3): 527-535.
40. Deeks ED. Disitamab vedotin: first approval. Drugs, 2021, 81(16): 1929-1935.
41. Xu Y, Wang Y, Gong J, 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, 24(4): 913-925.
42. Peng Z, Liu T, Wei J, et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase Ⅱ study. Cancer Commun (Lond), 2021, 41(11): 1173-1182.
43. Takegawa N, Nonagase Y, Yonesaka K, et al. DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase Ⅰ inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance. Int J Cancer, 2017, 141(8): 1682-1689.
44. Shitara K, Iwata H, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol, 2019, 20(6): 827-836.
45. Zhang J, Ji D, Shen W, et al. Phase Ⅰ trial of a novel anti-HER2 antibody-drug conjugate, ARX788, for the treatment of HER2-positive metastatic breast cancer. Clin Cancer Res, 2022: OF1-OF10.
46. Skidmore L, Sakamuri S, Knudsen NA, 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, 19(9): 1833-1843.
47. Zhang Y, Qiu MZ, Wang JF, et al. Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma. Cell Rep Med, 2022, 3(11): 100814. doi: 10.1016/ j.xcrm.2022.100814.
48. Capone E, Lattanzio R, Gasparri F, et al. EV20/NMS-P945, a novel thienoindole based antibody-drug conjugate targeting HER-3 for solid tumors. Pharmaceutics, 2021, 13(4): 483. doi: 10.3390/pharmaceutics13040483.
49. Prasad H, Mathew JKK, Visweswariah SS. Receptor guanylyl cyclase C and cyclic GMP in health and disease: perspectives and therapeutic opportunities. Front Endocrinol (Lausanne), 2022, 13: 911459. doi: 10.3389/fendo.2022.911459.
50. Almhanna K, Kalebic T, Cruz C, et al. Phase Ⅰ study of the investigational anti-guanylyl cyclase antibody-drug conjugate TAK-264 (MLN0264) in adult patients with advanced gastrointestinal malignancies. Clin Cancer Res, 2016, 22(20): 5049-5057.
51. Bang YJ, Takano T, Lin CC, et al. TAK-264 (MLN0264) in previously treated Asian patients with advanced gastrointestinal carcinoma expressing guanylyl cyclase C: results from an open-label, non-randomized phase 1 study. Cancer Res Treat, 2018, 50(2): 398-404.
52. Qiu S, Zhang J, Wang Z, et al. Targeting Trop-2 in cancer: recent research progress and clinical application. Biochim Biophys Acta Rev Cancer, 2023, 1878(4): 188902. doi: 10.1016/ j.bbcan.2023.188902.
53. Cardillo TM, Govindan SV, Sharkey RM, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2/SN-38 antibody-drug conjugate: characterization and efficacy in pancreatic, gastric, and other cancers. Bioconjug Chem, 2015, 26(5): 919-931.
54. Cheng Y, Yuan X, Tian Q, et al. Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front Oncol, 2022, 12: 951589. doi: 10.3389/fonc.2022.951589.
55. Fuentes-Antrás J, Genta S, Vijenthira A, et al. Antibody-drug conjugates: in search of partners of choice. Trends Cancer, 2023, 9(4): 339-354.

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