REFERENCES
1. He J, Zeng X, Wang C, Wang E, Li Y. Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies. MedComm. 2024;5:e671.
2. Strebhardt K, Ullrich A. Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer. 2008;8:473-80.
3. Sievers EL, Larson RA, Stadtmauer EA, et al.; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001;19:3244-54.
4. Senter PD, Sievers EL. The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat Biotechnol. 2012;30:631-7.
5. Amiri-Kordestani L, Blumenthal GM, Xu QC, et al. FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014;20:4436-41.
6. Modi S, Jacot W, Yamashita T, et al.; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9-20.
7. Meric-Bernstam F, Makker V, Oaknin 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. 2024;42:47-58.
8. Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22:790-800.
9. Yu EY, Petrylak DP, O’Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021;22:872-82.
10. Moore KN, Angelergues A, Konecny GE, et al.; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;389:2162-74.
11. Xi M, Zhu J, Zhang F, et al. Antibody-drug conjugates for targeted cancer therapy: recent advances in potential payloads. Eur J Med Chem. 2024;276:116709.
12. Jiang M, Li Q, Xu B. Spotlight on ideal target antigens and resistance in antibody-drug conjugates: strategies for competitive advancement. Drug Resist Updat. 2024;75:101086.
13. Loganzo F, Sung M, Gerber HP. Mechanisms of resistance to antibody-drug conjugates. Mol Cancer Ther. 2016;15:2825-34.
14. Zou Y, Yang A, Chen B, et al. crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer. Drug Resist Updat. 2024;77:101126.
15. Gandullo-Sánchez L, Pandiella A. An anti-EGFR antibody-drug conjugate overcomes resistance to HER2-targeted drugs. Cancer Lett. 2023;554:216024.
16. Saleh K, Khoury R, Khalife N, et al. Mechanisms of action and resistance to anti-HER2 antibody-drug conjugates in breast cancer. Cancer Drug Resist. 2024;7:22.
17. Walter RB, Gooley TA, van der Velden VH, et al. CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy. Blood. 2007;109:4168-70.
18. 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;99:628-38.
19. Ríos-Luci C, García-Alonso S, Díaz-Rodríguez E, et al. Resistance to the antibody-drug conjugate T-DM1 is based in a reduction in lysosomal proteolytic activity. Cancer Res. 2017;77:4639-51.
20. Linenberger ML, Hong T, Flowers D, et al. Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin. Blood. 2001;98:988-94.
21. Tang R, Cohen S, Perrot JY, et al. P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients. BMC Cancer. 2009;9:199.
22. Chen R, Hou J, Newman E, et al. CD30 downregulation, MMAE resistance, and MDR1 upregulation are all associated with resistance to brentuximab vedotin. Mol Cancer Ther. 2015;14:1376-84.
23. Robey RW, Lin B, Qiu J, Chan LL, Bates SE. Rapid detection of ABC transporter interaction: potential utility in pharmacology. J Pharmacol Toxicol Methods. 2011;63:217-22.
24. Shen DW, Fojo A, Chin JE, et al. Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. Science. 1986;232:643-5.
25. Robey RW, Honjo Y, van de Laar A, et al. A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2). Biochim Biophys Acta. 2001;1512:171-82.
26. Lee TD, Lee OW, Brimacombe KR, et al. A high-throughput screen of a library of therapeutics identifies cytotoxic substrates of P-glycoprotein. Mol Pharmacol. 2019;96:629-40.
27. Inglese J, Auld DS, Jadhav A, et al. Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries. Proc Natl Acad Sci U S A. 2006;103:11473-8.
28. Robey RW, Honjo Y, Morisaki K, et al. Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br J Cancer. 2003;89:1971-8.
29. Ishii M, Iwahana M, Mitsui I, et al. Growth inhibitory effect of a new camptothecin analog, DX-8951f, on various drug-resistant sublines including BCRP-mediated camptothecin derivative-resistant variants derived from the human lung cancer cell line PC-6. Anticancer Drugs. 2000;11:353-62.
30. Naito K, Takeshita A, Shigeno K, et al. Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines. Leukemia. 2000;14:1436-43.
31. Walter RB, Raden BW, Hong TC, Flowers DA, Bernstein ID, Linenberger ML. Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood. 2003;102:1466-73.
32. Walter RB, Raden BW, Thompson J, et al. Breast cancer resistance protein (BCRP/ABCG2) does not confer resistance to gemtuzumab ozogamicin and calicheamicin-gamma1 in acute myeloid leukemia cells. Leukemia. 2004;18:1914-7.
33. Cabaud O, Berger L, Crompot E, et al. Overcoming resistance to anti-nectin-4 antibody-drug conjugate. Mol Cancer Ther. 2022;21:1227-35.
34. Sun NY, Kumar S, Kim YS, et al. Identification of DLK1, a Notch ligand, as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma. bioRxiv. 2024.
35. Li WF, Chiang MF, Weng HC, et al. OBI-992, a novel TROP2-targeted antibody-drug conjugate, demonstrates antitumor activity in multiple cancer models. Mol Cancer Ther. 2025;24:163-75.
36. Chang TY, Lin CJ, Wen SN, et al. Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy. Sci Rep. 2025;15:8735.
37. Corbett S, Huang S, Zammarchi F, Howard PW, van Berkel PH, Hartley JA. The role of specific ATP-binding cassette transporters in the acquired resistance to pyrrolobenzodiazepine dimer-containing antibody-drug conjugates. Mol Cancer Ther. 2020;19:1856-65.
38. Yu SF, Zheng B, Go M, et al. A novel anti-CD22 anthracycline-based antibody-drug conjugate (ADC) That overcomes resistance to auristatin-based ADCs. Clin Cancer Res. 2015;21:3298-306.
39. Matsui H, Takeshita A, Naito K, et al. Reduced effect of gemtuzumab ozogamicin (CMA-676) on P-glycoprotein and/or CD34-positive leukemia cells and its restoration by multidrug resistance modifiers. Leukemia. 2002;16:813-9.
40. Kotono M, Kijima T, Takada-Owada A, et al. Increased expression of ATP-binding cassette transporters in enfortumab vedotin-resistant urothelial cancer. IJU Case Rep. 2024;7:173-6.
41. Tang R, Faussat AM, Perrot JY, et al. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML). BMC Cancer. 2008;8:51.
42. Marcelletti JF, Sikic BI. A clinical trial of zosuquidar plus gemtuzumab ozogamicin (GO) in relapsed or refractory acute myeloid leukemia (RR AML): evidence of efficacy based on leukemic blast P-glycoprotein functional phenotype. Cancer Chemother Pharmacol. 2023;92:369-80.
43. Chen R, Herrera AF, Hou J, et al. Inhibition of MDR1 overcomes resistance to brentuximab vedotin in hodgkin lymphoma. Clin Cancer Res. 2020;26:1034-44.
44. Thiruvengadam SK, Mei MG, Chen L, et al. Phase I trial of brentuximab vedotin plus cyclosporine in relapsed/refractory hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2024;24:724-31.e1.
45. Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer. 2018;18:452-64.
46. Giddens AC, Lee HH, Lu GL, et al. Analogues of DNA minor groove cross-linking agents incorporating aminoCBI, an amino derivative of the duocarmycins: Synthesis, cytotoxicity, and potential as payloads for antibody-drug conjugates. Bioorg Med Chem. 2016;24:6075-81.
47. Elgersma RC, Coumans RG, Huijbregts T, et al. Design, synthesis, and evaluation of linker-duocarmycin payloads: toward selection of HER2-targeting antibody-drug conjugate SYD985. Mol Pharm. 2015;12:1813-35.
48. Scribner JA, Brown JG, Son T, et al. Preclinical development of MGC018, a duocarmycin-based antibody-drug conjugate targeting B7-H3 for solid cancer. Mol Cancer Ther. 2020;19:2235-44.
49. van der Lee MMC, Groothuis PG, Ubink R, et al. The preclinical profile of the duocarmycin-based HER2-targeting ADC SYD985 predicts for clinical benefit in low HER2-expressing breast cancers. Mol Cancer Ther. 2015;14:692-703.
50. Turner N, Saura C, Aftimos P, et al.; TULIP Trial Investigators. Trastuzumab duocarmazine in pretreated human epidermal growth factor receptor 2-positive advanced or metastatic breast cancer: an open-label, randomized, phase III trial (TULIP). J Clin Oncol. 2025;43:513-23.
51. Lambert JM, Chari RV. Ado-trastuzumab emtansine (T-DM1): an antibody-drug conjugate (ADC) for HER2-positive breast cancer. J Med Chem. 2014;57:6949-64.
52. Roth JS, Guo H, Chen L, et al. Identification of antibody-drug conjugate payloads which are substrates of ATP-binding cassette drug efflux transporters. bioRxiv 2025. Available from: https://doi.org/10.1101/2025.05.22.651305 [accessed 12 Jan 2026].








