Trop2-targeted therapies in solid tumors: advances and future directions.

Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE

Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-

Antigens, Neoplasm*/immunology ; Cell Adhesion Molecules*/antagonists & inhibitors ; Cell Adhesion Molecules*/metabolism ; Immunoconjugates*/therapeutic use ; Immunoconjugates*/pharmacology ; Molecular Targeted Therapy*/methods ; Neoplasms*/drug therapy ; Neoplasms*/therapy; Humans ; Immunotherapy/methods ; Animals ; Cancer Vaccines/therapeutic use

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants in multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, the rapid development of various Trop2-targeted therapies, notably marked by the advent of the antibody-drug conjugate (ADC), revolutionized the outcome for patients facing Trop2-positive tumors with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides a comprehensive summary of advances in Trop2-targeted therapies, including ADCs, antibodies, multispecific agents, immunotherapy, cancer vaccines, and small molecular inhibitors, along with in-depth discussions on their designs, mechanisms of action (MOAs), and limitations. Additionally, we emphasize the clinical research progress of these emerging Trop2-targeted agents, focusing on their clinical application and therapeutic efficacy against tumors. Furthermore, we propose directions for future research, such as enhancing our understanding of Trop2's structure and biology, exploring the best combination strategies, and tailoring precision treatment based on Trop2 testing methodologies.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)

Eur J Nucl Med Mol Imaging. 2022 Feb;49(3):861-870. (PMID: 34519889)
Invest New Drugs. 2018 Oct;36(5):836-847. (PMID: 29333575)
Eur J Nucl Med Mol Imaging. 2024 Jan;51(2):380-394. (PMID: 37792026)
Nat Rev Clin Oncol. 2024 Mar;21(3):203-223. (PMID: 38191923)
Mol Cancer Ther. 2016 Nov;15(11):2698-2708. (PMID: 27582525)
Cancer Treat Rev. 2023 Jul;118:102572. (PMID: 37230055)
Eur J Nucl Med Mol Imaging. 2022 Dec;50(1):168-183. (PMID: 36063202)
Anticancer Res. 2016 Nov;36(11):5937-5944. (PMID: 27793919)
J Clin Oncol. 2023 Oct 10;41(29):4678-4687. (PMID: 37327461)
J Histochem Cytochem. 2011 Jul;59(7):701-10. (PMID: 21551320)
Drug Dev Res. 2021 Dec;82(8):1096-1110. (PMID: 34462935)
Neoplasia. 2021 Apr;23(4):415-428. (PMID: 33839455)
Int J Cancer. 2014 Mar 1;134(5):1239-49. (PMID: 23982827)
Cancer Biother Radiopharm. 2014 Oct;29(8):323-9. (PMID: 25226447)
Dev Dyn. 2015 Feb;244(2):99-109. (PMID: 25523132)
Am J Cancer Res. 2019 Aug 01;9(8):1846-1856. (PMID: 31497363)
J Immunother Cancer. 2021 Oct;9(10):. (PMID: 34599021)
Int J Mol Med. 2018 Jun;41(6):3671-3679. (PMID: 29568866)
Pharmacol Ther. 2022 Nov;239:108296. (PMID: 36208791)
Front Oncol. 2021 Jul 22;11:699889. (PMID: 34367983)
Genes Cancer. 2015 Mar;6(3-4):84-105. (PMID: 26000093)
Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2032-2042. (PMID: 31932422)
Int J Cancer Suppl. 1994;8:98-102. (PMID: 8194903)
Cancer Cell. 2022 Jun 13;40(6):559-564. (PMID: 35700704)
Int J Biol Macromol. 2023 Dec 31;253(Pt 6):127105. (PMID: 37769779)
ACS Nano. 2024 Jan 30;18(4):3087-3100. (PMID: 38235966)
Clin Cancer Res. 2011 May 15;17(10):3157-69. (PMID: 21372224)
Cancer Res. 2017 Oct 1;77(19):5384-5394. (PMID: 28819027)
Cancer Discov. 2021 Oct;11(10):2436-2445. (PMID: 34404686)
Oncogene. 2013 Jan 10;32(2):222-33. (PMID: 22349828)
Cancer Res. 1995 Dec 1;55(23 Suppl):5857s-5863s. (PMID: 7493360)
J Med Chem. 2023 Nov 9;66(21):14700-14715. (PMID: 37883180)
Int J Mol Sci. 2021 Sep 30;22(19):. (PMID: 34638982)
Mol Cancer Ther. 2014 Oct;13(10):2341-51. (PMID: 25053819)
PLoS One. 2014 May 13;9(5):e96993. (PMID: 24824621)
Mol Imaging Biol. 2015 Feb;17(1):94-101. (PMID: 25060065)
Mol Cancer Ther. 2021 Dec;20(12):2329-2340. (PMID: 34413126)
Front Oncol. 2022 Dec 23;12:951589. (PMID: 36620535)
Int J Biol Macromol. 2018 Apr 15;110:406-415. (PMID: 29055700)
Neoplasia. 2021 Sep;23(9):898-911. (PMID: 34320447)
Int J Mol Sci. 2022 Jul 19;23(14):. (PMID: 35887287)
Oncol Rep. 2021 Jul;46(1):. (PMID: 34013368)
Biochem Biophys Res Commun. 2019 Apr 30;512(2):276-282. (PMID: 30879767)
Protein Expr Purif. 2023 May;205:106242. (PMID: 36746324)
J Nucl Med. 2012 Oct;53(10):1625-32. (PMID: 22952342)
J Clin Oncol. 2022 Oct 10;40(29):3365-3376. (PMID: 36027558)
Mol Cancer Ther. 2023 Jun 1;22(6):790-804. (PMID: 36921314)
Front Immunol. 2023 Dec 11;14:1335252. (PMID: 38162667)
J Adv Res. 2024 Apr;58:193-210. (PMID: 37271476)
Front Pharmacol. 2023 Nov 10;14:1283247. (PMID: 38027003)
J Clin Oncol. 2021 Aug 1;39(22):2474-2485. (PMID: 33929895)
N Engl J Med. 2019 Feb 21;380(8):741-751. (PMID: 30786188)
Ann Oncol. 2021 Jun;32(6):746-756. (PMID: 33741442)
EMBO Mol Med. 2024 May;16(5):1143-1161. (PMID: 38565806)
Cancer Res. 2014 Nov 1;74(21):6216-23. (PMID: 25252911)
J Immunother. 2011 Apr;34(3):251-63. (PMID: 21389873)
Cancers (Basel). 2023 Jul 22;15(14):. (PMID: 37509383)
J Nanobiotechnology. 2023 Nov 6;21(1):410. (PMID: 37932752)
Mol Cancer. 2014 Mar 10;13:53. (PMID: 24606732)
Cancer Res. 1990 Feb 15;50(4):1330-6. (PMID: 2153458)
Oncogene. 2022 Mar;41(12):1795-1808. (PMID: 35132180)
J Am Chem Soc. 2023 Dec 27;145(51):28264-28275. (PMID: 38092662)
Biochem Biophys Res Commun. 2015 Mar 20;458(4):877-82. (PMID: 25701778)
Cancer Lett. 2023 Jul 10;566:216242. (PMID: 37217069)
Front Immunol. 2023 Dec 20;14:1332489. (PMID: 38179054)
Front Genet. 2024 Jan 05;14:1297367. (PMID: 38250577)
Cancer Cell. 2018 May 14;33(5):922-936.e10. (PMID: 29763625)
Ann Transl Med. 2022 May;10(9):501. (PMID: 35928735)
iScience. 2021 Sep 30;24(10):103190. (PMID: 34693228)
N Engl J Med. 2021 Apr 22;384(16):1529-1541. (PMID: 33882206)
J Clin Oncol. 2017 Jul 1;35(19):2141-2148. (PMID: 28291390)
Clin Cancer Res. 2017 Jul 1;23(13):3405-3415. (PMID: 28069724)
Biochim Biophys Acta Rev Cancer. 2023 Jul;1878(4):188902. (PMID: 37121444)
Nanomedicine. 2023 Jul;51:102687. (PMID: 37121458)
Mol Cancer Ther. 2023 Jan 3;22(1):102-111. (PMID: 36190986)
Proc Natl Acad Sci U S A. 1981 Aug;78(8):5147-50. (PMID: 7029529)
Hybridoma. 1992 Oct;11(5):539-45. (PMID: 1459581)
Expert Rev Anticancer Ther. 2019 Aug;19(8):673-679. (PMID: 31398063)

Keywords: Trop2; solid tumor; targeted therapies; therapeutic efficacy

0 (Antigens, Neoplasm)
0 (TACSTD2 protein, human)
0 (Cell Adhesion Molecules)
0 (Immunoconjugates)
0 (Cancer Vaccines)

Date Created: 20240701 Date Completed: 20240701 Latest Revision: 20240702

20240702

PMC11209721

10.7150/thno.98178

38948057